ORCID Profile
0000-0001-5439-1500
Current Organisations
University of Washington
,
Massey University - Wellington Campus
,
Fred Hutchinson Cancer Research Center
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Publisher: American Association for Cancer Research (AACR)
Date: 11-2005
DOI: 10.1158/1055-9965.EPI-05-0261
Abstract: Folate metabolism supports the synthesis of nucleotides as well as the transfer of methyl groups. Polymorphisms in folate-metabolizing enzymes have been shown to affect risk of colorectal neoplasia and other malignancies. Using data from a population-based incident case-control study (1,600 cases and 1,962 controls), we investigated associations between genetic variants in the reduced folate carrier (RFC), thymidylate synthase (TS), methionine synthase (MTR), and 5,10-methylenetetrahydrofolate reductase (MTHFR) and colon cancer risk. The TS enhancer region (TSER) variant was associated with a reduced risk among men [2rpt/2rpt versus 3rpt/3rpt wild-type odds ratio (OR), 0.7 95% confidence interval, 0.6-0.98] but not women. When combined genotypes for both TS polymorphisms (TSER and 3′-untranslated region 1494delTTAAAG) were evaluated, ORs for variant genotypes were generally below 1.0, with statistically significantly reduced risks among women. Neither MTR D919G nor RFC 80G& A polymorphisms were associated with altered colon cancer risk. Because folate metabolism is characterized by interrelated reactions, we evaluated gene-gene interactions. Genotypes resulting in reduced MTHFR activity in conjunction with low TS expression were associated with a reduced risk of colon cancer. When dietary intakes were taken into account, in iduals with at least one variant TSER allele (3rpt/2rpt or 2rpt/2rpt) were at reduced risk in the presence of a low folate intake. This study supports findings from adenoma studies indicating that purine synthesis may be a relevant biological mechanism linking folate metabolism to colon cancer risk. A pathway-based approach to data analysis is needed to help discern the independent and combined effects of dietary intakes and genetic variability in folate metabolism.
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.MATURITAS.2006.04.011
Abstract: Test the hypothesis that soy isoflavone supplementation preserves bone mineral density (BMD) in men and women. We conducted a controlled, parallel-arm, double-blinded trial with 145 participants, 50-80 years, with random assignment to soy beverage daily for 12 months. Active treatment (+ISO) received soy protein containing 83 mg isoflavones (45.6 mg genistein, 31.7 mg daidzein), aglycone units the comparison group (-ISO) received soy protein containing 3mg isoflavones. We measured BMD using dual-energy X-ray absorptiometry at the total hip and posterior-anterior spine (L1-L4) at baseline in 22 women and 123 men, and at 12 months in 13 women and 98 men. We used linear mixed models to test for an isoflavone effect on percentage BMD change from baseline in spine and hip. Among all participants, mean percent change in spine BMD (+/-S.E.) was 0.16+/-0.44 in -ISO (P=0.10) at 12 months. Treatment effects on spine BMD were significantly greater in women than men (P=0.01). At 12 months, in women, mean percent change was 0.58+/-0.70 in +ISO and -1.84+/-0.86 in -ISO (P=0.05) among men it was 1.32+/-0.53 in +ISO and 0.31+/-0.48 in -ISO (P=0.16). By comparison, percent change in hip BMD was similar in the treatment groups, and was not different between men and women. Mean percent change in hip BMD from baseline to 12 months was 0.54+/-0.38 in +ISO and -0.13+/-0.36 in -ISO (P=0.20) among all participants. Soy protein containing isoflavones showed a modest benefit in preserving spine, but not hip BMD in older women.
Publisher: Wiley
Date: 12-04-1999
DOI: 10.1002/(SICI)1097-0215(19990412)81:2<199::AID-IJC6>3.0.CO;2-7
Abstract: Although diet and its constituents have been studied extensively as risk factors for colon cancer, much less is known about how specific types of fluid influence colon cancer risk. In this study, we explored associations between colon cancer and total fluids, water and methylxanthine-containing beverages such as coffee, tea and cola data were obtained from 1,993 incident cases of colon cancer and 2,410 population-based controls living in California, Utah and Minnesota. Our primary objective was to determine the influence on associations of amount consumed, confounding and effect modification. We observed few important differences between colon cancer and fluid consumption for all subjects combined. Among men, low levels of coffee intake were associated with an increased risk of colon cancer relative to non-consumers of coffee (OR 1.32, 95% CI 1.02-1.67), while at high levels of consumption, an inverse association was observed (OR 0.81, 95% CI 0.58-1.12). The observed associations were only slightly influenced by consumption of water or other potential confounding factors, but changing the referent group to those consuming one cup of coffee per day or less resulted in a stronger association and a more significant inverse linear trend (OR 0.71, 95% CI 0.53-0.96). The associations with coffee and caffeine- and methylxanthine-containing beverages were strongest for proximal tumors in men. High levels of water intake, however, were protective for distal tumors (OR for men 0.68, 95% CI 0.49-0.96). Assessment of the impact of smoking on associations between colon cancer and coffee showed a significant interaction between smoking and coffee for both men and women.
Publisher: American Association for Cancer Research (AACR)
Date: 12-2007
DOI: 10.1158/0008-5472.CAN-07-3239
Abstract: Recent publications have reported that common variants on 8q24 are associated with both prostate and colorectal cancers (CRC). In addition, one of these studies (the ARCTIC study) initially observed an association with a single nucleotide polymorphism (SNP) on 9p24 that was not confirmed in some of their validation data sets. In the research described here, we conducted a case-unaffected sibling analysis using population- and clinic-based discordant sibships (N = 1,567 sibships) from the Colon Cancer Family Registry (Colon CFR) to investigate the associations between common variants at 9p24 and 8q24 and risk of CRC. We also evaluated whether these associations differed by age, family history, and tumor characteristics, including microsatellite instability and tumor site. Associations were estimated using conditional logistic regression, treating sibship as the matching factor. Analyses were adjusted for age and sex, and stratified by ascertainment source (population versus clinic). We observed an association between a SNP on 9p24 (rs719725) and risk of CRC in the population-based series (AA versus CC: odds ratios, 1.46 95% confidence interval, 1.06–2.02 AC versus CC: odds ratios, 1.50 95% confidence interval, 1.14–1.98 P = 0.011 on 2 df). In the population-based series, we also detected statistically significant associations between two SNPs on 8q24, rs10505477 and rs6983267, and risk of CRC (P = 0.005 and P = 0.002, respectively). There was no evidence of statistically significant heterogeneity by age at diagnosis, family history of CRC, microsatellite instability, or tumor site at either locus and no evidence of interaction between SNPs on 8q24 and 9p24. These data suggest that common variants may play important roles in the risk of CRC. [Cancer Res 2007 (23):11128–32]
Publisher: Springer Science and Business Media LLC
Date: 15-07-2011
Publisher: Wiley
Date: 07-2006
Abstract: Pancreatic juice is an exceptionally rich source of cancer-specific proteins shed from cancerous ductal cells into the pancreatic juice. Quantitative proteomic analysis of the proteins specific to pancreatic cancer juice has not previously been reported. We used isotope-code affinity tag (ICAT) technology and MS/MS to perform quantitative protein profiling of pancreatic juice from pancreatic cancer patients and normal controls. ICAT technology coupled with MS/MS allows the systematic study of the proteome and measures the protein abundance in pancreatic juice with the potential for development of biomarkers. A total of 105 proteins were identified and quantified in the pancreatic juice from a pancreatic cancer patient, of which 30 proteins showed abundance changes of at least twofold in pancreatic cancer juice compared to normal controls. Many of these proteins have been externally validated. This is the first comprehensive study of the pancreatic juice proteome by quantitative global protein profiling, and the study reveals numerous proteins that are shown for the first time to be associated with pancreatic cancer, providing candidates for diagnostic biomarkers. One of the identified proteins, insulin-like growth factor binding protein-2 was further validated by Western blotting to be elevated in pancreatic cancer juice and overexpressed in pancreatic cancer tissue.
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000114861
Abstract: i Background: /i Many epidemiologic studies examine the effects of single measurements of hormones, including those related to obesity such as insulin-like growth factors (IGFs) or leptin, on disease associations however, few studies have determined whether these single values accurately reflect measurements over time. i Methods: /i We examined the reproducibility of hormones associated with obesity, specifically leptin, IGF-I, and IGF-binding protein-3 (IGFBP-3). Two fasting blood s les, approximately four months apart, were collected from 38 participants from the Seattle metropolitan area leptin, IGF-I, and IGFBP-3 concentrations were measured in previously unthawed serum s les. Unadjusted and adjusted intraclass correlation coefficients (ICC) were calculated to assess reproducibility. i Results: /i Adjusting for age and sex, the ICCs for leptin, IGF-I, and IGFBP-3 were 0.73, 0.83 and 0.60, respectively. Weighted kappas yielded similar results. i Conclusion: /i These data suggest that for leptin, IGF-I, and IGFBP-3, a single fasting serum measurement can fairly reliably reflect the hormonal milieu over periods of months.
Publisher: Wiley
Date: 2005
DOI: 10.1002/SIM.2119
Abstract: Microarrays are used increasingly to identify genes that are truly differentially expressed in tissues under different conditions. Planning such studies requires establishing a s le size that will ensure adequate statistical power. For microarray analyses, false discovery rate (FDR) is considered to be an appropriate error measure. Several FDR-controlling procedures have been developed. How these procedures perform for such analyses has not been evaluated thoroughly under realistic assumptions. In order to develop a method of determining s le sizes for these procedures, it needs to be established whether these procedures really control the FDR below the pre-specified level so that the determined s le size indeed provides adequate power. To answer this question, we first conducted simulation studies. Our simulation results showed that these procedures do control the FDR at most situations but under-control the FDR when the proportion of positive genes is small, the most likely scenarios. Thus, these existing procedures can overestimate the power and underestimate the s le size. Accordingly, we developed a simulation-based method to provide more accurate estimates for power and s le size.
Publisher: BMJ
Date: 30-01-2008
Publisher: American Medical Association (AMA)
Date: 15-01-2003
Abstract: The increasing prevalence of obesity is a major public health concern. Physical activity may promote weight and body fat loss. To examine the effects of exercise on total and intra-abdominal body fat overall and by level of exercise. Randomized controlled trial conducted from 1997 to 2001. A total of 173 sedentary, overweight (body mass index > or =24.0 and >33% body fat), postmenopausal women aged 50 to 75 years who were living in the Seattle, Wash, area. Participants were randomly assigned to an intervention consisting of exercise facility and home-based moderate-intensity exercise (n = 87) or a stretching control group (n = 86). Changes in body weight and waist and hip circumferences at 3 and 12 months total body, intra-abdominal, and subcutaneous abdominal fat at 12 months. Twelve-month data were available for 168 women. Women in the exercise group participated in moderate-intensity sports/recreational activity for a mean (SD) of 3.5 (1.2) d/wk for 176 (91) min/wk. Walking was the most frequently reported activity. Exercisers showed statistically significant differences from controls in baseline to 12-month changes in body weight (-1.4 kg 95% confidence interval [CI], -2.5 to -0.3 kg), total body fat (-1.0% 95% CI, -1.6% to -0.4%), intra-abdominal fat (-8.6 g/cm2 95% CI, -17.8 to 0.9 g/cm2), and subcutaneous abdominal fat (-28.8 g/cm2) 95% CI, -47.5 to -10.0 g/cm2). A significant dose response for greater body fat loss was observed with increasing duration of exercise. Regular exercise such as brisk walking results in reduced body weight and body fat among overweight and obese postmenopausal women.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2008
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426030.V1
Abstract: Supplementary Table S3
Publisher: Massachusetts Medical Society
Date: 07-05-1998
DOI: 10.1056/NEJM199805073381913
Abstract: Respiratory epithelial adenomatoid hamartoma (REAH) is classified as a histopathologic diagnosis and often identified in sinus surgery for chronic rhinosinusitis (CRS). The purpose of this study was to clarify the frequency and predictors of REAH and prognosis of CRS with REAH in CRS cases. In the first study, we histologically reviewed sinonasal polyps and mucosal tissue specimens obtained from patients who underwent endoscopic sinus surgery (ESS) for CRS to reveal how many REAH were involved in ESS cases. We compared REAH and non-REAH groups in terms of preoperative symptoms and endoscopic, imaging and blood examination findings to elucidate predictors of REAH genesis. In the second study, we compared the data 3 months after surgery such as endoscopic and imaging findings and olfactory test to evaluate prognosis of CRS with REAH. The prevalence of REAH was 15.5% of all 304 cases in the first and second studies combined. Higher polyp score in the middle meatus was an independent predictor of the presence of REAH ( Higher polyp score in the middle meatus is an independent predictor of REAH. Olfactory function is difficult to recover after surgery in REAH patients because it is associated with recurrent polyps in the olfactory cleft.
Publisher: Cold Spring Harbor Laboratory
Date: 15-04-2021
DOI: 10.1101/2021.04.11.21255231
Abstract: Internationally, self-s ling for human papillomavirus (HPV) has been shown to increase participation in cervical-cancer screening. In Aotearoa New Zealand, there are long-standing ethnic inequalities in cervical-cancer screening, incidence, and mortality particularly for indigenous Māori women, as well as Pacific, and Asian women. We invited never- and markedly under-screened (≥5 years overdue) 30-69-year-old Māori, Pacific, and Asian women to participate in an open-label, three-arm, community-based, randomised controlled trial, with a nested sub-study. We aimed to assess whether two specific invitation methods for self-s ling improved screening participation over usual care among the least medically served populations. Women were in idually randomised 3:3:1 to: clinic-based self-s ling (CLINIC – invited to take a self-s le at their usual general practice) home-based self-s ling (HOME – mailed a kit and invited to take a self- s le at home) and usual care (USUAL – invited to attend a clinic for collection of a standard cytology s le). Neither participants nor research staff could be blinded to the intervention. In a subset of general practices, women who did not participate within three months of invitation were opportunistically invited to take a self-s le, either next time they attended a clinic or by mail. We randomised 3,553 women: 1,574 to CLINIC, 1,467 to HOME, and 512 to USUAL. Participation was highest in HOME (14.6% among Māori, 8.8% among Pacific, and 18.5% among Asian) with CLINIC (7.0%, 5.3% and 6.9%, respectively) and USUAL (2.0%, 1.7% and 4.5%, respectively) being lower. In fully adjusted models, participation was statistically significantly more likely in HOME than USUAL: Māori OR=9.7, (95%CI 3.0-31.5) Pacific OR=6.0 (1.8-19.5) and Asian OR=5.1 (2.4-10.9). There were no adverse outcomes reported. After three months, 2,780 non-responding women were invited to participate in a non-randomised, opportunistic, follow-on substudy. After 6 months,192 (6.9%) additional women had taken a self-s le. Using recruitment methods that mimic usual practice, we provide critical evidence that self-s ling increases screening among the groups of women (never and under-screened) who experience the most barriers in Aotearoa New Zealand, although the absolute level of participation through this population approach was modest. Follow-up for most women was routine but a small proportion required intensive support. ANZCTR Identifier: ACTRN12618000367246 (date registered 12/3/2018) www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371741& isReview=true UTN:U1111-1189-0531 Health Research Council of New Zealand (HRC 16/405) publichealth.massey.ac.nz/assets/Uploads/Study-protocol-V2.1Self-s ling-for-HPV-screening-a-community-trial.pdf
Publisher: American Society of Clinical Oncology (ASCO)
Date: 12-2041
Abstract: Oral mucositis is a nearly universal and often severe complication following hematopoietic cell transplantation (HCT). The objective of this study was to evaluate factors predicting oral mucositis severity among 133 patients undergoing allogeneic HCT for chronic myelogenous leukemia. All patients were transplanted between 1992 and 1999, were ≥ 18 years of age, received either cyclophosphamide/total-body irradiation (TBI) or busulfan/cyclophosphamide conditioning regimens, and received four doses of methotrexate for graft-versus-host disease prophylaxis post-transplant. Oral mucositis was measured by a trained examiner every 2 to 3 days using the Oral Mucositis Index (OMI). Multiple linear regression analysis was used to identify predictors of mean OMI during days 6 to 12, 1 to 18, and the maximum OMI score between days 1 to 18. TBI containing conditioning regimens, body mass index ≥ 25, and methylenetetrahydrofolate reductase 677 TT genotype were found to be predictive of higher mean OMI scores (P .05). Pretransplant multivitamin supplement use was associated with lower mean OMI scores compared to those who did not use supplements. Smoking status, race, pretransplant treatment with interferon-alfa or hydroxyurea, and patient/donor ABO compatibility were not associated with mean OMI scores. Patients who are scheduled to receive conditioning regimens containing TBI, have a pretransplant body mass index ≥ 25, or carry the methylenetetrahydrofolate reductase 677 TT genotype should be considered at greater risk of developing oral mucositis following HCT. Future studies should investigate whether multivitamin supplementation before HCT could reduce mucositis severity.
Publisher: Elsevier BV
Date: 03-2009
Publisher: Oxford University Press (OUP)
Date: 17-10-2008
DOI: 10.1093/AJE/KWM271
Publisher: Oxford University Press (OUP)
Date: 04-08-2015
DOI: 10.1093/AJE/KWV089
Publisher: American Association for Cancer Research (AACR)
Date: 11-2005
DOI: 10.1158/1055-9965.EPI-05-0270
Abstract: Genetic variability in DNA repair genes may contribute to differences in DNA repair capacity and susceptibility to cancer, especially in the presence of exposures such as smoking. In a Minnesota-based case-control study of cases with only adenomatous polyps (n = 384), only hyperplastic polyps (n = 191), or both types of polyps (n = 119) versus polyp-free controls (n = 601), we investigated the role of polymorphisms in the DNA repair genes O6-methylguanine methyltransferase (MGMT p.L84F and p.I143V), XPD (p.D312N and p.K751Q), and XPG (p.D1104H). MGMT polymorphisms were not associated with polyp risk. Overall, a homozygous variant XPD–combined genotype was associated with an increased risk of adenomatous polyps [odds ratio (OR), 1.57 95% confidence interval (95% CI), 1.04-2.38] and an XPGHH1104 genotype with a decreased risk of hyperplastic polyps (OR, 0.36 95% CI, 0.13-0.98). However, age stratification showed that the XPD association was present only in subjects ≥60 years old (OR, 3.77 95% CI, 1.94-7.35), whereas the XPG association was observed largely in subjects & years old (OR, 0.20 95% CI, 0.05-0.91). Smokers did not have a significantly increased risk of adenomatous polyps in the absence of synchronous hyperplastic polyps, except for subjects with a homozygous variant XPD genotype or a homozygous wild-type XPG genotype (OR, 3.93 95% CI, 1.68-9.21 and OR, 1.59 95% CI, 1.01-2.50, respectively). Smoking was associated with a statistically significant 2.5- to 6-fold increased risk of hyperplastic polyps for in iduals with most of the DNA repair genotypes. However, no substantial increase was observed among in iduals who were homozygous variant for XPG (1104HH OR, 1.38 95% CI, 0.25-7.65). Our data suggest that polymorphisms in DNA repair genes may be risk factors for colorectal neoplasia and that they may exacerbate the effects of exposures to carcinogens.
Publisher: Elsevier BV
Date: 10-1997
DOI: 10.1016/S1047-2797(97)00079-3
Abstract: We evaluated the performance of a telephone-administered food frequency questionnaire in a study of 190 men and women, 30-79 years of age, who participated as controls in a study of colon cancer. The telephone version of the questionnaire was modified from a longer food frequency questionnaire originally administered in person to each of the participants. One month later, the telephone questionnaire was administered to a subgroup of 190 participants and readministered to 169 members of the subgroup two weeks later to assess the reproducibility and comparative validity of the instrument. The unadjusted correlation for energy between the original in-person full food frequency questionnaire and the abbreviated telephone version was 0.69. The median energy intake from the telephone version was 17% lower in men and 23% lower in women. The energy and sex-adjusted correlation coefficients for other nutrients ranged from 0.45 for vitamin E to 0.78 for fiber. The intraclass correlation coefficients to measure reproducibility ranged from 0.62 for animal protein to 0.83 for folate. These data indicate that this brief, telephone-administered questionnaire is reproducible and provides a ranking of nutrient intake comparable to that provided by a full in-person interview.
Publisher: Cambridge University Press (CUP)
Date: 03-1981
DOI: 10.1079/BJN19810104
Abstract: 1. The hypothesis that soya-bean saponins, by binding bile salts in the gastrointestinal lumen, are responsible for some of the plasma-cholesterol-lowering effect of soya-bean preparations, was tested. In a double-blind crossover study 50 g soya-bean flour/d, containing either 22 or 4 g saponins/kg (adjusted by ethanol extraction) was incorporated in biscuits as a substitute for biscuits or bread into the diet of ten outpatient hypercholesterolaemic men over two consecutive 4-week study periods. The diet was monitored to ensure constancy, saponin-rich foods excluded, faeces collected for bile acid and neutral sterol analysis, and blood taken for plasma lipoprotein lipid analysis. 2. Neither diet had any effect on cholesterol in any plasma lipoprotein fraction, on fasting plasma triglyceride, or on faecal bile acids and neutral sterols. 3. These results suggested that soya-bean saponins are not responsible for the hypocholesterolaemic effect of soya-bean products.
Publisher: Wiley
Date: 19-01-2006
DOI: 10.1002/IJC.21791
Abstract: The transcriptional activity of the vitamin D receptor (VDR) gene is regulated, at least in part, by the androgen receptor (AR) gene. We evaluate how the number of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in conjunction with vitamin D, sunshine exposure and VDR. Studies of colon (1,580 cases and 1,968 controls) and rectal (797 cases and 1,016 controls) cancer were used. Vitamin D intake and average hours of sunshine exposure interacted with AR genotype in men. Men with low vitamin D intake or low levels of sunshine exposure who had 23+ CAG repeats of the AR gene had the greatest risk of colon cancer. ORs for men with 23 or more CAG repeats of the AR gene and in the lowest tertile of vitamin D intake or sunshine exposure were 1.71 (95% CI 1.14, 2.56) and 1.51 (95% CI 1.09, 2.09). Men with high levels of sunshine exposure were at reduced risk of developing rectal cancer if they had 23 or more CAG repeats (OR 0.62 95% CI 0.39, 0.97) than if they had fewer than 23 CAG repeats. The FF genotype of the Fok1 VDR gene was associated with reduced risk of colon cancer among women with any allele of 23+ CAG repeats (OR 0.62 95% CI 0.44, 0.88), whereas men with the LL/bb VDR genotypes were at reduced risk of rectal cancer if they also had 23+ CAG repeats (OR 0.71 95% CI 0.48, 1.05) relative to men with fewer than 23 CAG repeats of the AR gene. These data provide support for the role of vitamin D and sunshine exposure in the etiology of colorectal cancer and suggest that AR gene may modulate the association.
Publisher: Elsevier BV
Date: 06-2006
Publisher: Springer Science and Business Media LLC
Date: 11-1991
DOI: 10.1007/BF00054304
Abstract: In 2004 an outbreak of avian influenza of the H7N3 subtype occurred among poultry in British Columbia, Canada. We report compliance with recommended protective measures and associated human infections during this outbreak. We sought voluntary participation by anyone (cullers, farmers and their families) involved in efforts to control the poultry outbreak. Recruitment was by advertisements at the worker deployment site, in local media and through newsletters sent directly to farmers. Sera were tested for antibody to H7N3 by microneutralization assay. A subset of 16 sera (including convalescent sera from 2 unprotected workers with conjunctivitis from whom virus had been isolated) was further tested by Western blot and routine and modified hemagglutination inhibition assays. A total of 167 people (20% to 25% of all workers) participated between May 7 and July 26, 2004. Of these, 19 had experienced influenza-like illness and 21 had experienced red or watery eyes. There was no significant association between illness reports and exposure to infected birds. Among 65 people who entered barns with infected birds, 55 (85%) had received influenza vaccine, 48 (74%) had received oseltamivir, and 55 (85%), 54 (83%) and 36 (55%) reported always wearing gloves, mask or goggles, respectively. Antibody to the H7 subtype was not detected in any sera. During the BC outbreak, compliance with recommended protective measures, especially goggles, was incomplete. Multiple back-up precautions, including oseltamivir prophylaxis, may prevent human infections and should be readily accessible and consistently used by those involved in the control of future outbreaks of avian influenza in poultry. Localized human avian influenza infections may not result in serologic response despite confirmed viral detection and culture.
Publisher: Informa UK Limited
Date: 07-2011
DOI: 10.1080/19338244.2010.539636
Abstract: Changes in immune status have been suggested as a possible biologic mechanism by which particulate matter (PM) air pollution could lead to adverse health effects. The authors studied associations between ambient PM₂.₅ and immune status among 115 postmenopausal, overweight women in the greater Seattle, Washington, area. The authors evaluated 3-day, 30-day, and 60-day average PM₂.₅ values in relation to inflammation markers (C-reactive protein, serum amyloid A, interleukin-6) and functional assays of cellular immunity (natural killer cell cytotoxicity, T-lymphocyte proliferation) at 3 time points for each woman during 1 year. Three-day averaged PM₂.₅ was inversely associated with anti-CD3-stimulated lymphocyte proliferation. There were no notable associations between the inflammation markers and PM₂.₅. If additional studies confirm our findings, then future health effect assessments for PM₂.₅ should consider changes in cellular immunity as an endpoint that may lead to overt clinical disease.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2013
Publisher: American Association for Cancer Research (AACR)
Date: 05-2005
Publisher: American Association for Cancer Research (AACR)
Date: 03-2005
DOI: 10.1158/1055-9965.EPI-04-0510
Abstract: Prostaglandin H synthase 2 (PTGS2) or cyclooxygenase-2 (COX-2) has been shown to play a key role in the regulation of inflammation, and its inhibition is associated with a reduced risk of colon cancer. The PTGS2 (COX-2) −765G & C promoter variant is located in a putative SP1 binding site and reduces PTGS2 expression. In a Minnesota-based case-control study of cases with adenomatous (n = 494) or hyperplastic polyps (n = 186) versus polyp-free controls (n = 584), we investigated the role of the PTGS2 −765G & C promoter polymorphism. Multiple logistic regression analysis was used, adjusting for age, body mass index, caloric intake, alcohol, fiber, sex, hormone use, and smoking. For colorectal adenoma, odds ratios (OR) compared with PTGS2 −765GG as reference were GC 1.00 [95% confidence interval (95% CI), 0.74-1.35] and CC 0.53 (95% CI, 0.22-1.28). For hyperplastic polyps, the comparable adjusted odds ratios were GC 0.97 (95% CI, 0.65-1.46) and CC 0.24 (95% CI, 0.05-1.11). Risk associated with the −765G & C variant differed by aspirin or other nonsteroidal anti-inflammatory drug (NSAID) use. Among nonusers of aspirin or other NSAIDs, the CC genotype conferred a significant decrease in risk of adenoma (OR, 0.26 95% CI, 0.07-0.89). Use of aspirin or other NSAIDs reduced risk of adenoma only among those with the −765GG (wild type) and possibly −765CG genotypes (OR, 0.66 95% CI, 0.48-0.92 and OR, 0.64 95% CI, 0.40-1.02, respectively). These data suggest that COX-2 expression or activity may be beneficially suppressed, and risk of colorectal polyps reduced, by aspirin or other NSAIDs in PTGS2 −765GG (wild type) in iduals and by the −765 CC variant genotype in nonusers of NSAIDs.
Publisher: Elsevier BV
Date: 11-1994
Abstract: Few current data are available regarding factors associated with participation in cancer screening examinations in the general population. To identify factors associated with participation in cancer screening examinations, random population s les of 25- to 74-year-old men and women in six various-sized communities in three upper-Midwestern states (n = 4,915) were surveyed in 1987-1989. Multivariate-adjusted means were calculated and compared using analysis of covariance. Statistically significant (P < 0.05) strong predictors (other than age and sex) of ever having had a specific cancer screening test were as follows (the numbers in parentheses following each listed association are the absolute maximum differences in mean proportions among the levels of the predictors): (1) rectal examination: higher education (14%) (2) fecal occult blood testing: higher education (6%) and never smoker (5%) (3) sigmoidoscopy: higher income (7%) and higher education (6%) and (5) mammography: higher income (25%), higher education (8%), and a positive family history of breast cancer (7%). There were no strong predictors (out of nine) of ever having had a Papanicolaou smear or a breast self-examination. The largest differences among the population for participation in cancer screening examinations involves income and the two most expensive cancer screening tests: higher income is a strong predictor of having a mammogram and, to a lesser extent, of having a sigmoidoscopy. The most consistent predictor of participation in cancer screening examinations across all cancer screening tests is education: higher education is a predictor of having each kind of cancer screening test.
Publisher: Wiley
Date: 07-09-2012
Publisher: Oxford University Press (OUP)
Date: 21-04-2007
Publisher: American Association for Cancer Research (AACR)
Date: 09-2012
Publisher: Oxford University Press (OUP)
Date: 15-10-2008
DOI: 10.1093/JNCI/DJN326
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2014
DOI: 10.1038/AJG.2014.233
Publisher: American Association for Cancer Research (AACR)
Date: 14-08-2018
DOI: 10.1158/0008-5472.CAN-18-0326
Abstract: Nonsteroidal anti-inflammatory drugs’ (NSAID) use has consistently been associated with lower risk of colorectal cancer however, studies showed inconsistent results on which cohort of in iduals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on colorectal cancer risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions. Regular use of any NSAID, aspirin, or nonaspirin NSAIDs was significantly associated with a lower risk of colorectal cancer within almost all subgroups. However, smoking status and BMI were found to modify the NSAID–colorectal cancer association. Aspirin use was associated with a 29% lower colorectal cancer risk among never-smokers [odds ratios (OR) = 0.71 95% confidence intervals (CI): 0.64–0.79], compared with 19% and 17% lower colorectal cancer risk among smokers of pack-years below median (OR, 0.81 95% CI, 0.71–0.92) and above median (OR, 0.83 95% CI, 0.74–0.94), respectively (P interaction = 0.048). The association between any NSAID use and colorectal cancer risk was also attenuated with increasing BMI (P interaction = 0.075). Collectively, these results suggest that obese in iduals and heavy smokers are unlikely to benefit as much as other groups from the prophylactic effect of aspirin against colorectal cancer. Significance: Obesity and heavy smoking attenuate the benefit of aspirin use for colorectal cancer prevention. Cancer Res 78(16) 4790–9. ©2018 AACR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2004
DOI: 10.1097/01.EDE.0000091604.32542.97
Abstract: Physical activity is associated with a reduced risk of several chronic diseases. Although there is considerable published research on methods to assess current or recent recreational physical activity, there are few short, self-administered questionnaires designed to assess long-term physical activity. We developed a one-page questionnaire to capture data on usual recreational physical activity during the preceding 10 years. This questionnaire was used in a cohort study of adults age 50 to 75 years residing in western Washington state. To examine the measurement characteristics of this questionnaire, we compared metabolic equivalent task (MET)-hours derived from this short questionnaire to MET-hours estimated from a detailed comparison interview in a subs le (n = 217) and to current body mass index (BMI weight in kilograms/height in square meters) in the full s le of 57,811 persons. The age- and sex-adjusted partial Pearson correlation coefficient for total recreational activity between the 2 instruments was 0.68. In the full cohort, BMI was inversely correlated with physical activity as assessed by the one-page questionnaire (r = -0.22). This short questionnaire measures long-term physical activity at a level of precision appropriate to the examination of associations in studies of physical activity and disease.
Publisher: Oxford University Press (OUP)
Date: 24-06-2015
DOI: 10.1093/JNCI/DJV170
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22420551.V1
Abstract: Table S1 shows similar results of interactions between BMI/smoking and NSAID use, using multiple imputation for missing values.
Publisher: BMJ
Date: 12-1993
Abstract: The cross sectional study describes the prevalence of infection with Helicobacter pylori as determined by a serodiagnostic assay in over 3000 asymptomatic subjects, in two age groups 25-34 years and 55-64 years, from 17 geographically defined populations in Europe, North Africa, North America, and Japan, using a common protocol for blood collection and serological testing. In all populations combined, the prevalence of infection was higher in the older age group (62.4%) than in the younger age group (34.9%). There was no difference in prevalence of infection between men and women. Subjects with higher education had considerably lower levels of infection (34.1%) compared with subjects with education up to secondary level (46.9%) or those with primary education only (61.6%). This trend was confined to the older of the two age groups. In contrast a trend of increasing prevalence of infection with increasing body mass index was confined to the younger of the two age groups. There was no effect of smoking or alcohol consumption on the prevalence of infection after adjusting for the other risk factors. There was considerable variation in the prevalence of infection between the 17 populations but, within populations, low education standard was consistently and positively associated with the prevalence of infection.
Publisher: Elsevier BV
Date: 06-2004
Publisher: Oxford University Press (OUP)
Date: 1984
DOI: 10.1093/IJE/13.2.240
Abstract: The epidemiological evidence relating alcohol consumption and lung cancer is reviewed. Four correlation studies have shown a relationship between alcohol, particularly beer, consumption and lung cancer. Beer consumption was a risk factor in one case-control study. Eight out of ten prospective studies show alcoholics and high alcohol consumers to be at greater risk of lung cancer. Not all of the increased risk in these studies is explainable in terms of confounding by tobacco consumption. There is some animal evidence which supports the effects of alcohol on the likelihood of developing lung cancer.
Publisher: Wiley
Date: 1997
DOI: 10.1002/(SICI)1098-2272(1997)14:4<365::AID-GEPI3>3.0.CO;2-2
Abstract: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15 ) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3 high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.
Publisher: Oxford University Press (OUP)
Date: 04-10-1995
Abstract: In the past decade, significant progress has been made in understanding the genetic component of familial cancers. Genes associated with familial colon and breast cancers have recently been isolated and molecular diagnostic tests are expected to become available in the near future. Clinicians now have the opportunity to recognize and counsel in iduals with elevated risk of cancer by identifying risk factors and genes associated with cancer predisposition. The rapid advances in molecular technology are a direct challenge to the medical community and cancer centers to supply specialized clinical services for familial cancers. We sought to ascertain the activities of cancer centers in the development of programs and the provision of genetic services for familial cancer. We surveyed 41 centers with National Cancer Institute (NCI) cancer center support grants. One half of the centers responding (17 of 34) reported that they provide some genetic services for familial cancer. About one half of these 17 centers (eight [57%] of 14 the three remaining clinics that responded had incomplete information on this indicator) see a variety of patient types on a small scale (fewer than 100 patients per year), and most provide four basic clinical evaluations: medical evaluation, cancer risk assessment, genetic counseling, and pedigree analysis. Staffing of each center varied widely, as did the types of screening services offered (including molecular diagnostic testing). Several centers (six [35%] of 17) indicated that they were in the developmental stages for serving familial cancer patients, and many seem to be increasing their activities in this area. The remaining 17 NCI-supported centers that responded, however, currently provide no genetic services for familial cancers. The results of this survey suggest that there is interest in developing clinical programs for familial cancers by NCI-supported cancer centers, but most of these programs are in developmental stages. A base line has been established to monitor future progress for the provision of cancer genetic services.
Publisher: Springer Science and Business Media LLC
Date: 06-2007
DOI: 10.1038/NRC2146
Abstract: Morphogenetic fields organize tissue morphology in the embryo. By analogy, morphostatic fields maintain normal cell behaviour and normal tissue microarchitecture in the adult. The most prominent feature of cancer is the disruption of tissue microarchitecture. Cancer occurs much more frequently when morphostatic influences fail (metaplasia) or at the junction of two different morphostatic fields. This Review will describe what we know about morphostats and morphostasis, discuss the evidence for the role of disruption of morphostasis in malignancy, and address some testable hypotheses.
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: To test the hypothesis that childhood acute lymphoblastic leukemia (ALL) is associated with allergic disorders. We compared the histories of selected allergic disorders (asthma, hay fever, food or drug allergies, eczema, and hives) of 1842 cases of ALL with those of 1986 in idually matched controls. The histories of the allergic disorders among siblings of cases and controls were also compared. The combined history of any one or more of the five allergic disorders evaluated was associated with a significant reduced risk of ALL (adjusted OR = 0.7, 95% CI 0.6-0.8), as were histories of four specific allergic disorders (asthma, hay fever, food or drug allergies, and eczema). The combined history of any one or more of the five allergic disorders among any of the siblings of the study subjects also revealed a significantly inverse association (adjusted OR = 0.9, 95% CI 0.8-1.0). The results from this study, in agreement with most previous studies on adult cancer, suggest that allergic disorders may be associated with a reduced risk of childhood ALL.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2008
DOI: 10.1158/1055-9965.EPI-08-0571
Abstract: Based on the high volume of bacteria and viruses that the intestine is exposed to and the importance of infectious agents in some gastrointestinal and anogenital cancers, it is not surprising the many studies have evaluated the association between colorectal cancer and infectious agents. This review highlights investigations of four agents in relation to colorectal cancer. Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus have all been evaluated as possible etiologic agents for colorectal cancer. For each of these agents, a review of possible mechanisms for carcinogenesis and epidemiologic evidence is discussed, and future directions for research are proposed. (Cancer Epidemiol Biomarkers Prev 2008 (11):2970–79)
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-07-2010
Publisher: American Association for Cancer Research (AACR)
Date: 09-2014
DOI: 10.1158/1055-9965.EPI-14-0062
Abstract: Background: Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer. Prior research has evaluated the presence of gene–environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. Methods: Data on 9,160 cases and 9,280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, postmenopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons. Results: None of the permutation-adjusted P values reached statistical significance. Conclusions: The associations between recently identified genetic susceptibility loci and colorectal cancer are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors. Impact: Results suggest no evidence of strong gene–environment interactions involving the recently identified 16 susceptibility loci for colorectal cancer taken one at a time. Cancer Epidemiol Biomarkers Prev 23(9) 1824–33. ©2014 AACR.
Publisher: Public Library of Science (PLoS)
Date: 03-04-2013
Publisher: American Medical Association (AMA)
Date: 18-02-1998
Abstract: To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13 P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.
Publisher: Public Library of Science (PLoS)
Date: 22-06-2011
Publisher: Elsevier BV
Date: 02-2010
Publisher: Springer Science and Business Media LLC
Date: 05-07-2007
Abstract: Gene-set analysis evaluates the expression of biological pathways, or a priori defined gene sets, rather than that of in idual genes, in association with a binary phenotype, and is of great biologic interest in many DNA microarray studies. Gene Set Enrichment Analysis (GSEA) has been applied widely as a tool for gene-set analyses. We describe here some critical problems with GSEA and propose an alternative method by extending the in idual-gene analysis method, Significance Analysis of Microarray (SAM), to gene-set analyses (SAM-GS). Using a mouse microarray dataset with simulated gene sets, we illustrate that GSEA gives statistical significance to gene sets that have no gene associated with the phenotype (null gene sets), and has very low power to detect gene sets in which half the genes are moderately or strongly associated with the phenotype (truly-associated gene sets). SAM-GS, on the other hand, performs very well. The two methods are also compared in the analyses of three real microarray datasets and relevant pathways, the erging results of which clearly show advantages of SAM-GS over GSEA, both statistically and biologically. In a microarray study for identifying biological pathways whose gene expressions are associated with p53 mutation in cancer cell lines, we found biologically relevant performance differences between the two methods. Specifically, there are 31 additional pathways identified as significant by SAM-GS over GSEA, that are associated with the presence vs. absence of p53 . Of the 31 gene sets, 11 actually involve p53 directly as a member. A further 6 gene sets directly involve the extrinsic and intrinsic apoptosis pathways, 3 involve the cell-cycle machinery, and 3 involve cytokines and/or JAK/STAT signaling. Each of these 12 gene sets, then, is in a direct, well-established relationship with aspects of p53 signaling. Of the remaining 8 gene sets, 6 have plausible, if less well established, links with p53 . We conclude that GSEA has important limitations as a gene-set analysis approach for microarray experiments for identifying biological pathways associated with a binary phenotype. As an alternative statistically-sound method, we propose SAM-GS. A free Excel Add-In for performing SAM-GS is available for public use.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2008
Publisher: American Association for Cancer Research (AACR)
Date: 09-2012
DOI: 10.1158/1055-9965.EPI-12-0651
Abstract: Background: Oncogenic human papillomaviruses (HPV) are sexually transmitted and linked to several epithelial malignancies, but an association between HPV and colorectal neoplasia is not established. Previously, we reported a three-fold increase in the odds of colorectal hyperplastic polyps associated with oncogenic HPV seropositivity in men but detected no HPV DNA in colorectal tissues from these same men. Methods: To test the reproducibility of our prior HPV antibody results and to explore the hypothesis that colorectal hyperplastic polyps may be associated with sexual behavior in men, we conducted a case–control study of hyperplastic polyps and antibodies to eight oncogenic HPV types (including 16 and 18), Herpes simplex virus-2 (HSV-2), and hepatitis C virus (HCV). Study participants were men, ages 30–74 years, enrolled in the Minnesota Cancer Prevention Research Unit Polyp Study who had an index colonoscopy from 1991 to 1994, and received a diagnosis of hyperplastic polyps (n = 97) or were polyp-free (n = 184). Plasma was assessed for antibodies to the eight oncogenic HPV types, HSV-2, and HCV using a bead-based multiplex assay. Results: The adjusted ORs for the association between hyperplastic polyps and seropositivity to oncogenic HPV (all eight types combined) was 0.84 [95% confidence interval (CI), 0.44–1.58 for HSV-2, OR, 0.98, 95% CI, 0.48–1.99 and for HCV, OR, 0.61 95% CI, 0.11–3.26]. Conclusions: Our study suggested no association between colorectal hyperplastic polyps and antibodies to specific sexually transmitted infections (STI) in men. Impact: Factors associated with STIs are unlikely to play a role in the etiology of colorectal hyperplastic polyps in men. Cancer Epidemiol Biomarkers Prev 21(9) 1599–601. ©2012 AACR.
Publisher: Massachusetts Medical Society
Date: 11-12-1997
Publisher: Wiley
Date: 15-10-2008
DOI: 10.1002/CNCR.23829
Abstract: Breast cancer is the most common invasive cancer in women globally, and it affects more than 1 million women worldwide each year. It is a preventable disease in part, and primary care providers and public health programs play a key role in providing cancer preventive care. There are several health behaviors that may reduce the risk of breast cancer, including prolonged lactation regular physical activity avoiding overweight, obesity, and lifetime weight gain avoiding excess alcohol intake avoiding prolonged use of exogenous hormone therapy and avoiding excessive radiation. These behaviors, although they have not been proven in clinical trials to reduce risk, are likely to be beneficial information on them can be provided as a prevention strategy in countries of erse means, although the methods of information delivery and follow-up will depend on financial and personnel resources. Many of these health behaviors can reduce the risk for other chronic diseases and, thus, may be of great interest for general public health. In high resource level countries, additional prevention methods are available for high-risk women, including selective estrogen response modulators and, for women at very high risk, bilateral prophylactic mastectomy and bilateral oophorectomy. Most women can benefit from advice and preventive care for reducing their risk for breast cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/0008-5472.23814641.V1
Abstract: supplementary materials
Publisher: Informa UK Limited
Date: 04-2011
Publisher: No publisher found
Date: 2002
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426024
Abstract: Supplementary Table S4
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426021
Abstract: Supplementary Table S5
Publisher: American Association for Cancer Research (AACR)
Date: 03-2009
DOI: 10.1158/1055-9965.EPI-08-0878
Abstract: Family history is a strong predictor of colorectal cancer risk however, a diagnosis of colorectal cancer among first-degree relatives has not been systematically investigated as a function of the colorectal cancer molecular subtypes related to tumor microsatellite instability (MSI) status. We investigated whether the observable familial colorectal cancer risks differed according to tumor MSI subtypes, stratified as MSI-High (& % instability), MSI-Low (& % instability), and MSS (no instability). Data from 3,143 population-based colorectal cancer cases from five institutions were assessed for family history according to the Amsterdam criteria and the Bethesda guidelines, age at diagnosis, sex, tumor location, and MSI status. The distribution of patient characteristics by MSI status was compared using polytomous logistic regression. Overall, 2.8% colorectal cancer cases met the Amsterdam criteria and 37% met the Bethesda guidelines. There were 14% MSI-High, 13% MSI-Low, and 73% MSS colorectal cancers. MSI-High (P & 0.0001) and MSI-Low tumors (P = 0.01) were more proximally located than MSS tumors. MSI-High tumors were more common among females (P & 0.001). The highest proportion of MSI-High tumors occurred in cases & years of age whereas the age-dependent distribution of MSI-Low tumors was unchanged. MSI-High tumors showed a statistically significant association with increasing numbers of first-degree relatives with colorectal cancer (P = 0.002) this association disappeared, however, when MSI-High cases meeting Amsterdam criteria were removed from the analysis. MSI-Low tumors did not show a similar association with family history of colorectal cancer. Familial risk associated with MSI-High tumors is primarily driven by the Amsterdam-criteria patients. MSI-Low tumors may represent a distinct subtype of colorectal cancer with respect to certain epidemiologic variables studied here. (Cancer Epidemiol Biomarkers Prev 2009 (3):967–75)
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/0008-5472.23814632.V1
Abstract: Summary of G × BMI analyses using 1DF, two-step, and 3DF analyses.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2007
DOI: 10.1158/1055-9965.EPI-07-0648
Abstract: Background: Family studies have served as a cornerstone of genetic research on colorectal cancer. Materials and Methods: The Colorectal Cancer Family Registry (Colon CFR) is an international consortium of six centers in North America and Australia formed as a resource to support studies on the etiology, prevention, and clinical management of colorectal cancer. Differences in design and s ling schemes ensures a resource that covers the continuum of disease risk. Two separate recruitment strategies identified colorectal cancer cases: population-based (incident case probands identified by cancer registries all six centers) and clinic-based (families with multiple cases of colorectal cancer presenting at cancer family clinics three centers). At this time, the Colon CFR is in year 10 with the second phase of enrollment nearly complete. In phase I recruitment (1998-2002), population-based s ling ranged from all incident cases of colorectal cancer to a subs le based on age at diagnosis and/or family cancer history. During phase II (2002-2007), population-based recruitment targeted cases diagnosed before the age of 50 years are more likely attributable to genetic factors. Standardized protocols were used to collect information regarding family cancer history and colorectal cancer risk factors, and biospecimens were obtained to assess microsatellite instability (MSI) status, expression of mismatch repair proteins, and other molecular and genetic processes. Results: Of the 8,369 case probands enrolled to date, 2,602 reported having one or more colorectal cancer–affected relatives and 799 met the Amsterdam I criteria for Lynch syndrome. A large number of affected (1,324) and unaffected (19,816) relatives were enrolled, as were population-based (4,108) and spouse (983) controls. To date, 91% of case probands provided blood (or, for a few, buccal cell) s les and 75% provided tumor tissue. For a selected s le of high-risk subjects, lymphocytes have been immortalized. Nearly 600 case probands had more than two affected colorectal cancer relatives, and 800 meeting the Amsterdam I criteria and 128, the Amsterdam II criteria. MSI testing for 10 markers was attempted on all obtained tumors. Of the 4,011 tumors collected in phase I that were successfully tested, 16% were MSI-high, 12% were MSI-low, and 72% were microsatellite stable. Tumor tissues from clinic-based cases were twice as likely as population-based cases to be MSI-high (34% versus 17%). Seventeen percent of phase I proband tumors and 24% of phase II proband tumors had some loss of mismatch repair protein, with the prevalence depending on s ling. Active follow-up to update personal and family histories, new neoplasms, and deaths in probands and relatives is nearly complete. Conclusions: The Colon CFR supports an evolving research program that is broad and interdisciplinary. The greater scientific community has access to this large and well-characterized resource for studies of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2007 (11):2331–43)
Publisher: Wiley
Date: 08-12-2014
DOI: 10.1002/IJC.29360
Publisher: American Medical Association (AMA)
Date: 06-06-2007
Publisher: American Association for Cancer Research (AACR)
Date: 03-2005
DOI: 10.1158/1055-9965.EPI-04-0602
Abstract: Background: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). Methods: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. Results: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+) odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL−). Conclusion: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426015
Abstract: Supplementary Table S7
Publisher: Elsevier BV
Date: 09-2004
DOI: 10.1016/J.JCLINEPI.2004.01.005
Abstract: The Childhood Cancer Survivor Study is a retrospective cohort study that was initiated to explore late effects of childhood cancer and its therapies. We evaluated the characteristics of those requiring tracing and factors that influenced tracing success. Medical record review identified 20,051 eligible in iduals from 25 institutions in the United States and Canada. Of these, 13,021 had a current address in the medical record at the treating institution, and 7,030 had an incorrect address and required tracing by a commercial firm. Tracing was successful for 4,188 persons (60%). Younger age at contact, shorter length of time since last contact, having a middle initial available, an uncommon last name, and socioeconomic factors were found to predict successful tracing. Compared to those with a current address available in medical records, subjects successfully traced were less likely to have accessed health care during the previous 2 years and more likely to be current smokers, obese, and to report moderate to severe impairments (pain, functional status, and activity). These findings provide an empirical basis concerning determinants and predictors of tracing success. If tracing had not been performed in this cohort, spurious associations may have been obtained for some health outcomes of interest.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2008
DOI: 10.1158/1055-9965.EPI-08-0512
Abstract: Microsatellite instability (MSI) occurs in 10% to 20% of colorectal cancers (CRC) and has been attributed to both MLH1 promoter hypermethylation and germline mutation in the mismatch repair (MMR) genes. We present results from a large population- and clinic-based study of MLH1 methylation, immunohistochemistry, and MMR germline mutations that enabled us to (a) estimate the prevalence of MMR germline mutations and MLH1 methylation among MSI-H cases and help us understand if all MSI-H CRC is explained by these mechanisms and (b) estimate the associations between MLH1 methylation and sex, age, and tumor location within the colon. MLH1 methylation was measured in 1,061 population-based and 172 clinic-based cases of CRC. Overall, we observed MLH1 methylation in 60% of population-based MSI-H cases and in 13% of clinic-based MSI-H cases. Within the population-based cases with MMR mutation screening and conclusive immunohistochemistry results, we identified a molecular event in MMR in 91% of MSI-H cases: 54% had MLH1 methylation, 14% had a germline mutation in a MMR gene, and 23% had immunohistochemistry evidence for loss of a MMR protein. We observed a striking age difference, with the prevalence of a MMR germline mutation more than 4-fold lower and the prevalence of MLH1 methylation more than 4-fold higher in cases diagnosed after the age of 50 years than in cases diagnosed before that age. We also determined that female sex is an independent predictor of MLH1 methylation within the MSI-H subgroup. These results reinforce the importance of distinguishing between the underlying causes of MSI in studies of etiology and prognosis. (Cancer Epidemiol Biomarkers Prev 2008 (11):3208–15)
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426018
Abstract: Supplementary Table S6
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426012
Abstract: Supplementary Text
Publisher: Springer Science and Business Media LLC
Date: 04-1982
DOI: 10.1038/296780A0
Publisher: American Association for Cancer Research (AACR)
Date: 28-03-2012
DOI: 10.1158/1055-9965.EPI-11-1168
Abstract: Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue s les from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation–negative (RR = 0.83 95% CI, 0.66–1.06 P = 0.14) and KRAS mutation–positive (RR = 0.82 95% CI, 0.58–1.16 P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation–negative, distal colorectal tumors (RR = 0.64 95% CI, 0.43–0.96 P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMH therapy. These data suggest that PMH therapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits for KRAS mutation–negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy–related CRC risk reduction. Cancer Epidemiol Biomarkers Prev 21(4) 681–4. ©2012 AACR.
Publisher: Elsevier BV
Date: 04-1997
DOI: 10.1016/S1047-2797(97)00012-4
Abstract: Specific events in the mother's reproductive history and certain birth characteristics have been associated with childhood leukemia. Few studies have explored these associations specifically in infants. The Children's Cancer Group (CCG) conducted three separate case-control studies of childhood leukemia that involved similar methodologies and data collection. Data from interviews of the mothers of a total of 303 children diagnosed with leukemia at 1 year of age or younger and their matched controls (n = 468) were available from the three studies. These data included maternal reproductive history (stillbirths, abortions, and miscarriages) and certain birth characteristics of the index child. Compared with controls, cases were significantly more likely to be female (P < 0.01) and were more often heavier at birth (particularly cases diagnosed after 6 months of age (odds ratio, 4.18 95% confidence interval, 1.75-10.02)). Overall, there were no statistically significant differences between cases and controls in regard to maternal report of any type of previous fetal loss. Finally, being a later-born child was associated with an increased risk of acute myeloid leukemia but not of acute lymphoblastic leukemia. The relationships among birthweight, prior fetal loss, and risk of infant leukemia appear to be complex. Further studies of infant leukemia that incorporate molecular as well as epidemiologic data may help to elucidate these differences.
Publisher: Oxford University Press (OUP)
Date: 13-06-2015
DOI: 10.1093/JNCI/DJV160
Publisher: Springer Science and Business Media LLC
Date: 10-2005
DOI: 10.1007/S10552-005-2702-3
Abstract: Insulin-like growth factors (IGFs) play an important role in cell proliferation and apoptosis, and recent epidemiologic studies have suggested that circulating IGF-1 and IGF binding protein-3 (IGFBP-3) may be related to colorectal, breast, and prostate cancer risk. The purpose of this analysis was to investigate the role of various personal and lifestyle factors in the inter-in idual variation of circulating IGF-1 and IGFPB-3. We measured plasma levels of IGF-1 and IGFBP-3 in a sequential s le of 333 population-based control subjects enrolled in the Seattle Colorectal Cancer Family Registry from August 1999 through December 2001, who had provided a blood s le. Total IGF-1 and IGFBP-3 were measured from plasma s les using ELISA assays. Interviewer-administered questionnaires collected data on various personal and lifestyle factors. Multivariate-adjusted linear regression was used to assess the associations between specific personal and lifestyle factors with IGF-1 and IGFBP-3 levels. Age, body mass index, and postmenopausal hormone use were statistically significantly inversely related to IGF-1 concentrations, and milk consumption was significantly positively related to IGF-1 levels. Only age was significantly related to circulating IGFBP-3. Although the sources of inter-in idual variation of IGF-1 and IGFB-3 are not yet fully understood, this analysis provides some insights into factors that may contribute.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2015
DOI: 10.1158/1055-9965.EPI-14-1253
Abstract: Background: There is substantial evidence that use of NSAIDs reduces the risk of colorectal cancer, but no subgroup has been identified for which the chemoprevention effect outweighs the risk of side effects. Methods: We tested the interaction between NSAID use and multiple risk factors on colorectal cancer risk in the VITAL cohort. A total of 73,458 in iduals ages 50 to 76 years completed a questionnaire between 2000 and 2002, and 674 incidental colorectal cancer cases were identified through 2010. Results: In stratified analysis, high use of any type of NSAIDs (4+ days/week for 4+ years) was statistically significantly associated with a lower risk of colorectal cancer across all subgroups stratified by sex, body mass index, physical activity, smoking, alcohol intake, screening, and dietary factors. There was a suggestion of stronger associations among men, obese in iduals, and heavier drinkers however, none of these tests for interaction reached statistical significance. The associations were almost identical for subjects with higher overall colorectal cancer risk scores [HR, 0.62 95% confidence interval (CI), 0.49–0.79] and those with lower risk scores (HR, 0.61 95% CI, 0.42–0.88). Differential effects by cancer subsites and stages were tested. NSAID use was associated with a greater risk reduction of proximal colon cancer versus distal (P for difference = 0.06) and distant stage versus local (P for difference = 0.04). Conclusion: The association between high use of NSAIDs and colorectal cancer risk does not differ significantly among subgroups. Impact: Our results suggest that NSAIDs have a generally beneficial role in colorectal cancer prevention, largely unmodified by other exposures. Cancer Epidemiol Biomarkers Prev 24(4) 727–35. ©2015 AACR.
Publisher: Massachusetts Medical Society
Date: 02-06-2011
DOI: 10.1056/NEJMC1104343
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: Epidemiologic studies on calcium, vitamin D and colon cancer are inconsistent, whereas experimental studies more regularly show a protective effect. To evaluate potential sources of inconsistencies, data from a large case-control study were analyzed, stratifying on potential effect modifiers. Data were collected by certified interviewers in Northern California, Utah and Minnesota. Analyses included 1993 incident colon cancer cases and 2410 population-based controls. Multivariate logistic regression models included age, sex, BMI, family history, physical activity, intake of energy, dietary fiber, aspirin and NSAIDs. Dietary calcium was inversely associated with colon cancer risk in men (OR highest vs lowest quintile = 0.6, 95% CI = 0.5-0.9) and women (OR = 0.6, 95% CI = 0.4-0.9). No statistically significant associations were observed for dietary vitamin D or sunshine exposure. Consumption of total low-fat dairy products was associated with a statistically significantly decreased risk in men and women (ORs highest vs lowest category of intake = 0.8 and 0.7 respectively). Calcium supplement use was inversely associated with risk in both sexes (ORs use vs non-use = 0.8). Vitamin D supplements were inversely associated with risk in men (OR = 0.5) and women (OR = 0.6) but confidence limits included 1.0. These data provide additional support of an inverse association between high levels of calcium intake and colon cancer risk.
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: Postmenopausal hormone use and risk of breast cancer by histopathology was examined in a large multi-centered population-based case-control study. Women younger than 75 years newly diagnosed with invasive breast cancer between 1988 and 1991 were identified from statewide tumour registries in Wisconsin, Massachusetts, New H shire, and Maine. Only postmenopausal women were included in this analysis. Breast cancer cases (lobular (n = 219), ductal, NOS (n = 2172), and specific ductal subtypes (n = 242)) were compared with randomly selected population controls (n = 3179) using adjusted multi-variable polytomous logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for each histology. Lobular carcinoma was associated with recent (within 2 years) estrogen therapy (OR: 1.8, 95% CI: 1.0-3.4) and recent use of combined estrogen-plus-progestin therapy (OR:3.6, 95%CI: 1.8-7.6). Risk of ductal carcinoma was not associated with recent use of either estrogen alone (OR: 0.9, 95% CI: 0.7-1.2) or combined therapy (OR:0.9, 95% CI: 0.6-1.3). No associations were found with ductal subtypes. The association between postmenopausal hormone use and risk of breast cancer may depend on histopathology. Of particular interest is the association between combined hormone therapy and increased risk of lobular carcinoma. This lesion is increasingly common but, nonetheless, comprises fewer than 10% of invasive breast cancers.
Publisher: Wiley
Date: 23-03-2007
DOI: 10.1002/IJC.22603
Abstract: Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. We investigated the role of functional polymorphisms in the TS 5'-UTR promoter enhancer region (TSER, 3 or 2 repeats of a 28-bp sequence) and the 3'-UTR (1494delTTAAAG) and their association with colon tumor characteristics, including tumor stage and acquired mutations in p53, Ki-ras and microsatellite instability. Data from a population-based incident case-control colon cancer study in northern California, Utah and Minnesota (1,206 cases, 1,962 controls) was analyzed using unordered polytomous logistic regression models. In both men and women, in iduals with variant TS alleles were at reduced risk of having an advanced stage tumor (metastatic disease: OR = 0.35, 95% CI: 0.2-0.6 vs. wildtype TSER and 3'-UTR). Stage-adjusted survival did not differ by genotype. Men with 1 or 2 variant alleles in both the TSER and 3'-UTR genotypes had a 50% reduced risk of a p53-positive tumor (OR = 0.5, 95% CI: 0.3-0.9 vs. homozygous wildtype TSER and 3'-UTR). Women with 1 or 2 variant alleles for either the TSER or 3'-UTR polymorphism had reduced risk of having any colon tumor that did not vary by mutation status. This study provides some support for associations between TS genotype and colon cancer tumor characteristics.
Publisher: American Association for Cancer Research (AACR)
Date: 30-05-2023
DOI: 10.1158/0008-5472.CAN-22-3713
Abstract: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2005
Publisher: American Medical Association (AMA)
Date: 27-01-1993
Publisher: American Association for Cancer Research (AACR)
Date: 15-10-2020
DOI: 10.1158/0008-5472.CAN-20-0168
Abstract: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.
Publisher: American Physiological Society
Date: 06-2008
DOI: 10.1152/JAPPLPHYSIOL.01349.2007
Abstract: Cross-sectional studies suggest that moderate physical activity is associated with enhanced resting immune function however, few randomized controlled trials have investigated this link. We investigated the effect of 12-mo aerobic exercise, relative to stretching control, on in vitro immune function in a randomized, controlled trial of 115 postmenopausal, overweight, or obese sedentary women, aged 50–75 yr. The exercise goal was ≥45 min/day, 5 days/wk. Control women participated in 1 day/wk stretching classes. Immune markers (natural killer cell cytotoxicity, T-lymphocyte proliferation, immune cell counts and phenotypes, and serum immunoglobulins) were assessed at baseline, 3 mo, and 12 mo under strict blood-draw criteria. General estimation equations evaluated intervention effects at 3 and 12 mo, controlling for baseline. Of the 115 women who began the trial, blood s les were available from 109 at 3 mo (95%) and 108 at 12 mo (94%). From baseline to 12 mo, the exercise group participated in 87% of the prescribed physical activity minutes per week and increased maximal O 2 uptake by 13.8% controls experienced no change in fitness. The main outcomes, natural killer cell cytotoxicity and T-lymphocyte proliferation, did not differ between groups at 3 and 12 mo. Secondary outcome and subgroup (e.g., stratification by baseline categories of body mass index, immune status, C-reactive protein, and age) analyses did not show any clear patterns of association. This 12-mo randomized, controlled trial showed no effect of aerobic exercise on in vitro immune function, despite excellent retention, high adherence, and demonstrable efficacy of the exercise intervention.
Publisher: Springer Science and Business Media LLC
Date: 02-2001
DOI: 10.1038/35052575
Abstract: You come onto the court prepared for tennis but your partner seems to be ready for rugby. Neither of you is at all sure what it is that your opponent wants to play. The only recourse is to teach each other the rules of your own game and then decide whether you can collectively invent a new sport. Welcome to the dialogue at the intersections of epidemiology with genetics and genomics.
Publisher: Elsevier BV
Date: 2006
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.AMJMED.2006.06.033
Abstract: Our aim was to assess the effect of a moderate-intensity, year-long exercise program on the risk of colds and other upper respiratory tract infections in postmenopausal women. A total of 115 overweight and obese, sedentary, postmenopausal women in the Seattle area participated. Participants were randomly assigned to the moderate-intensity exercise group or the control group. The intervention consisted of 45 minutes of moderate-intensity exercise 5 days per week for 12 months. Control participants attended once-weekly, 45-minute stretching sessions. Questionnaires asking about upper respiratory tract infections in the previous 3 months were administered quarterly during the course of the year-long trial. Poisson regression was used to estimate the effect of exercise on colds and other upper respiratory tract infections. Over 12 months, the risk of colds decreased in exercisers relative to stretchers (P = .02): In the final 3 months of the study, the risk of colds in stretchers was more than threefold that of exercisers (P = .03). Risk of upper respiratory tract infections overall did not differ (P = .16), yet may have been biased by differential proportions of influenza vaccinations in the intervention and control groups. This study suggests that 1 year of moderate-intensity exercise training can reduce the incidence of colds among postmenopausal women. These findings are of public health relevance and add a new facet to the growing literature on the health benefits of moderate exercise.
Publisher: Springer Science and Business Media LLC
Date: 1997
Abstract: Of 2895 women who self-detected an incident breast cancer that required surgery, peaks in month of detection occurred in spring and late autumn (p = 0.012). For the subset of cases for whom receptor status was available, there was a highly significant seasonal variation in detection only for those with ER-negative tumors. Further investigations into seasonality and breast cancer detection may be warranted.
Publisher: BMJ
Date: 10-03-2015
Publisher: Springer Science and Business Media LLC
Date: 07-11-2007
Abstract: Multiple data-analytic methods have been proposed for evaluating gene-expression levels in specific biological pathways, assessing differential expression associated with a binary phenotype. Following Goeman and Bühlmann's recent review, we compared statistical performance of three methods, namely Global Test, ANCOVA Global Test, and SAM-GS, that test "self-contained null hypotheses" Via. subject s ling. The three methods were compared based on a simulation experiment and analyses of three real-world microarray datasets. In the simulation experiment, we found that the use of the asymptotic distribution in the two Global Tests leads to a statistical test with an incorrect size. Specifically, p-values calculated by the scaled χ 2 distribution of Global Test and the asymptotic distribution of ANCOVA Global Test are too liberal, while the asymptotic distribution with a quadratic form of the Global Test results in p-values that are too conservative. The two Global Tests with permutation-based inference, however, gave a correct size. While the three methods showed similar power using permutation inference after a proper standardization of gene expression data, SAM-GS showed slightly higher power than the Global Tests. In the analysis of a real-world microarray dataset, the two Global Tests gave markedly different results, compared to SAM-GS, in identifying pathways whose gene expressions are associated with p53 mutation in cancer cell lines. A proper standardization of gene expression variances is necessary for the two Global Tests in order to produce biologically sensible results. After the standardization, the three methods gave very similar biologically-sensible results, with slightly higher statistical significance given by SAM-GS. The three methods gave similar patterns of results in the analysis of the other two microarray datasets. An appropriate standardization makes the performance of all three methods similar, given the use of permutation-based inference. SAM-GS tends to have slightly higher power in the lower α -level region (i.e. gene sets that are of the greatest interest). Global Test and ANCOVA Global Test have the important advantage of being able to analyze continuous and survival phenotypes and to adjust for covariates. A free Microsoft Excel Add-In to perform SAM-GS is available from www.ualberta.ca/~yyasui/homepage.html .
Publisher: American Association for Cancer Research (AACR)
Date: 02-2008
DOI: 10.1158/1055-9965.EPI-07-2608
Abstract: Disturbances in DNA methylation are a characteristic of colorectal carcinogenesis. Folate-mediated one-carbon metabolism is essential for providing one-carbon groups for DNA methylation via DNA methyltransferases (DNMTs). Alcohol, a folate antagonist, could adversely affect one-carbon metabolism. In a case-control study of colorectal polyps, we evaluated three single nucleotide polymorphisms (−149C& T, −283T& C, −579G& T) in the promoter region of the DNMT3b gene, and a functional polymorphism in the coding region of the alcohol dehydrogenase ADH1C gene, ADH1C *2. Cases had a first diagnosis of colorectal adenomatous (n = 530) or hyperplastic (n = 202) polyps at the time of colonoscopy, whereas controls were polyp-free (n = 649). Multivariate logistic regression analysis was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI). There were no significant main associations between the DNMT3b or ADH1C polymorphisms and polyp risk. However, DNMT3b −149TT was associated with an increase in adenoma risk among in iduals with low folate and methionine intake (OR, 2.00 95% CI, 1.06-3.78, P interaction = 0.10). The ADH1C *2/*2 genotype was associated with a possibly elevated risk for adenomatous polyps among in iduals who consumed & g of alcohol/d (OR, 1.95 95% CI, 0.60-6.30), whereas in iduals who were wild-type for ADH1C were not at increased risk of adenoma (P interaction = 0.01). These gene-diet interactions suggest that polymorphisms relevant to DNA methylation or alcohol metabolism may play a role in colorectal carcinogenesis in conjunction with a high-risk diet. (Cancer Epidemiol Biomarkers Prev 2008 (2):330–8)
Publisher: Proceedings of the National Academy of Sciences
Date: 16-01-2003
Abstract: The role of missense changes in BRCA1 in breast cancer susceptibility has been difficult to establish. We used comparative evolutionary methods to identify potential functionally important amino acid sites in exon 11 and missense changes likely to disrupt gene function, aligning sequences from 57 eutherian mammals and categorizing amino acid sites by degree of conservation. We used Bayesian phylogenetic analyses to determine relationships among orthologs and identify codons evolving under positive selection. Most conserved residues occur in a region with the highest concentration of protein-interacting domains. Rapidly evolving residues are concentrated in the RAD51-interacting domain, suggesting that selection is acting most strongly on the role of BRCA1 in DNA repair. Investigation of the functional role of missense changes in breast-cancer susceptibility should focus on 38 missense changes in conserved and 3 in rapidly evolving regions of exon 11.
Publisher: Public Library of Science (PLoS)
Date: 26-12-2012
Publisher: Wiley
Date: 13-08-2004
DOI: 10.1002/CNCR.20520
Abstract: One of the most serious late effects of treatment for childhood cancer is the occurrence of subsequent malignancy. Survivors of Hodgkin disease (HD), in particular, have been shown to be at high risk of subsequent malignancy, the occurrence of which has been associated strongly with exposure to radiotherapy. In the current study, the authors investigated the association between polymorphisms in 3 genes--glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and XRCC1, with roles in protection from a variety of DNA-damaging agents-and the risk of subsequent malignancy in 650 survivors of HD enrolled in the Childhood Cancer Survivor Study who had received radiotherapy. In iduals lacking GSTM1 but not GSTT1 were at increased risk of any subsequent malignancy (odds ratio [OR], 1.5 95% confidence interval [CI], 1.0-2.3), and for subsequent cancer within the radiation field (OR, 1.4 95% CI, 0.9-2.1). A nonsignificant increased risk of thyroid carcinoma was observed in in iduals lacking either GSTM1 (OR, 2.9 95% CI, 0.8-10.9) or GSTT1 (OR, 3.7 95% CI, 0.6-23.5). In iduals having the genotype of the arginine/glutamine polymorphism at codon 399 in the XRCC1 gene (R399) showed a nonsignificant increased risk of breast carcinoma compared with those without (OR, 1.4 95% CI, 0.7-2.7), and a nonsignificant decreased risk against a subsequent thyroid carcinoma (OR, 0.6 95% CI, 0.2-1.6). No differences in genotype frequencies were observed between survivors with basal cell carcinoma when compared with survivors without a subsequent cancer. These data illustrated the potential value of incorporating the collection of genomic DNA in longitudinal cohort studies of populations with well defined, potentially carcinogenic exposures. Evaluation of additional genetic polymorphisms in this cohort may help define genes that influence in idual sensitivity to radiotherapy.
Publisher: Elsevier BV
Date: 10-1996
DOI: 10.1016/S0002-8223(96)00273-8
Abstract: Early educator well-being is increasingly understood as a critical ingredient of high-quality early education and care. The COVID-19 pandemic has threatened educator well-being by exacerbating existing stressors and introducing novel stressors to all aspects of early educators' lives, and early educators have had differential access to resources to cope with these new circumstances. Using survey data collected between April and June 2020 with a s le of 666 early educators in community-based center, family child care, Head Start, and public school prekindergarten programs across Massachusetts, we document the pandemic's initial influence on educators' sense of well-being. Adopting an ecological perspective, we consider educator-, program-, and community-level factors that may be associated with reported changes in well-being. Most educators indicated that their mental and financial well-being had been affected. These changes were not systematically associated with most contextual factors, although there was clear evidence of variability in reported impacts by provider type. These findings underscore the need to support educator well-being, as well as to create policy solutions that meet the heterogeneous needs of this essential workforce.
Publisher: American Medical Association (AMA)
Date: 27-04-2005
Publisher: BMJ
Date: 17-10-2022
Publisher: Springer Science and Business Media LLC
Date: 08-07-2007
DOI: 10.1038/NG2089
Abstract: Using a multistage genetic association approach comprising 7,480 affected in iduals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected in iduals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected in iduals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend P = 1.41 x 10(-8)) and 1.14 (trend P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected in iduals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend 95% confidence interval (c.i.): 1.07-1.26 P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23 P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426018.V1
Abstract: Supplementary Table S6
Publisher: Springer Science and Business Media LLC
Date: 10-05-2011
DOI: 10.1038/BJC.2011.172
Publisher: Elsevier BV
Date: 12-2004
DOI: 10.1016/J.YPMED.2004.04.017
Abstract: Few studies have examined the long-term adherence to a yearlong exercise intervention among postmenopausal women. We examined the patterns of adherence to a yearlong exercise intervention and the influence of demographic, physiologic, and psychosocial variables on patterns of adherence among 173 sedentary, overweight, postmenopausal women. We collected demographic, physical activity (PA), physiologic, psychosocial, and medical history information at baseline and 12 months. The exercise prescription consisted of at least 45 min of moderate-intensity exercise 5 days/week for 12 months. We calculated several adherence variables. Associations between baseline variables and adherence levels were assessed in bivariate analyses and in multiple regression models. Women randomized to the exercise group (N = 87) participated in moderate-intensity sports or recreational PA on 3.7 +/- 1.4 days/week (79% of the prescribed 5 days/week) for 171 +/- 88 min/week (87% of the prescribed 225 min/week) over the yearlong trial period. Sixty-eight percent of the exercisers had a yearlong average PA level exceeding the national recommendation of 150 min/week. Being in the preparation stage vs. the contemplation stage of the transtheoretical model and a history of participating in any sports or recreational PA were significant predictors of adherence. Our findings provide important information for the design of future PA interventions and health promotion programs.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2013
Publisher: Wiley
Date: 03-10-2002
DOI: 10.1002/CNCR.10859
Abstract: Few studies have examined the risk of childhood acute lymphoblastic leukemia (ALL) associated with parental medication use. As part of a large case-control study conducted by the Children's Cancer Group, we evaluated the association between maternal and paternal medication use and the risk of ALL in offspring. Information on selected medication use in the year before and during the index pregnancy was obtained by telephone interview. Participants included 1842 children of 14 years or younger with newly diagnosed and immunophenotypically defined ALL and 1986 in idually matched controls. Data were analyzed using logistic regression models and stratified by immunophenotypes of ALL and age at diagnosis of cases. After adjusting for potential confounders and other medication use, we found that maternal use of vitamins (odds ratio [OR] = 0.7, 99% confidence interval [CI]: 0.5-1.0) and iron supplements (OR = 0.8, 99% CI: 0.7-1.0) only during the index pregnancy was associated with a decreased risk of ALL. Parental use of hetamines or diet pills and mind-altering drugs before and during the index pregnancy was related to an increased risk of childhood ALL, particularly among children where both parents reported using these drugs (OR = 2.8, 99% CI: 0.5-15.6 for hetamines or diet pills, OR = 1.8, 99% CI: 1.1-3.0 for mind-altering drugs). Stratified analyses showed that maternal use of antihistamines or allergic remedies and parental use of mind-altering drugs were strongly associated with infant ALL, whereas patterns of association between childhood ALL and parental medication use did not influence markedly the immunophenotypic subgroup of ALL. The findings of this study suggest that certain parental medication use immediately before and during the index pregnancy may influence risk of ALL in offspring.
Publisher: Oxford University Press (OUP)
Date: 21-12-1994
Abstract: Previous studies have suggested that cancers of the breast and prostate cluster in families and that the presence of both diseases in a family may be associated with increased risk of breast cancer. Our purpose was to evaluate whether 1) prostate cancer aggregates in families with postmenopausal breast cancer, 2) families with cancers of the breast and prostate are the same ones as families with cancers of the breast and ovary, and 3) a family history of prostate cancer is associated with increased risk of postmenopausal breast cancer. We analyzed data from a large prospective cohort study of Iowa women that were (at baseline) aged 55-69 years in 1986. At the third follow-up survey in 1992, self-reported data on family history of breast, ovarian, and prostate cancers in parents and siblings were provided by 30,883 women. Additional information was collected to ascertain whether the age-of-onset of breast cancer in mothers or sisters was before or after the age of 45 years. Cancer occurrence was documented using the State Health Registry of Iowa. History of prostate cancer in their father or a brother was reported by 3384 (11.0%) of the women, and a total of 4090 women (13.2%) reported breast cancer in their mother or a sister. A positive family history of both cancers was reported by 556 women, significantly (two-sided P < .001) greater than the 457 women expected if the family histories were independent. The aggregation of breast, prostate, and ovarian cancers was reported by 22 participants, greater than the 2.7 expected (two-sided P < .0001). During 6 years of follow-up, 578 breast cancers were identified in the cohort at risk. Compared with women without a family history of either cancer, women with a family history of breast cancer had a relative risk (RR) of 1.37 (95% confidence interval [CI] = 1.06-1.79) if the affected relative had onset after the age of 45 years, and an RR of 1.71 (95% CI = 1.13-2.61) if the affected relative had onset at or before the age of 45. A family history of prostate cancer in the absence of a family history of breast cancer was associated with an RR of 1.19 (95% CI = .90-1.56). However, a family history of both breast and prostate cancers was associated with RRs of 2.06 (95% CI = 1.23-3.45) and 2.35 (95% CI = .97-5.67) for breast cancer onset in relatives of greater than 45 and less than or equal to 45 years, respectively. These observations are concordant with recent reports that suggest a shared familial risk (inherited or environmental) for these hormone-dependent malignancies.
Publisher: American Association for Cancer Research (AACR)
Date: 12-2007
DOI: 10.1158/1055-9965.EPI-07-2611
Abstract: Studies suggest that polymorphisms of the vitamin D receptor (VDR) gene may influence colorectal cancer risk. In this study, we examine the association of the CDX2 VDR polymorphism (rs11568820) located in the 5′-untranslated region of the gene, and VDR haplotypes, including this polymorphism, with colon and rectal cancer using data from two large case-control studies of colon (N = 1,574 cases and 1,970 controls) and rectal (n = 791 cases and 999 controls) cancer. The frequency of the A allele of the CDX2 polymorphism was 19% among non–Hispanic white, 21% among Hispanic, 76% among African American, and 47% among Asian controls. The CDX2 polymorphism was not independently associated with either colon or rectal cancer, nor did it modify associations of dietary calcium, vitamin D, or fat with colon or rectal cancer. However, the bLFA haplotype which occurred in 6.5% of non–Hispanic white participants and 41.2% of African American participants was associated with an increased risk of colon cancer, and an odds ratio of 2.4 [95% confidence intervals (CI), 2.45 (1.38-4.38)]. The BSfG haplotype was associated with a 1.61 (95% CI, 1.05-2.49) increased risk of rectal but not colon cancer, whereas the BSFA haplotype was associated with a significantly reduced risk of rectal (odds ratio, 0.71 95% CI, 0.52-0.97) but not colon cancer. These data suggest that haplotype analysis that encompasses different domains of the VDR gene might further our understanding of associations between the VDR gene and colon and rectal cancer. (Cancer Epidemiol Biomarkers Prev 2007 (12):2752–5)
Publisher: Springer Science and Business Media LLC
Date: 1998
Abstract: This paper reviews the epidemiologic data of associations between physical activity and cancer risk, describes potential mechanisms for a physical activity cancer link, and proposes future directions for research. We reviewed English-language published papers on physical activity and cancer through Medline searches for epidemiologic studies, and through references on in idual reports. We reviewed general texts on effects of exercise on human biology and applied the concepts to the biology of cancer in humans to describe potential mechanisms for a physical activity-cancer association. Considerable epidemiologic evidence has accrued linking increased physical activity with reduced occurrence of cancers of the breast and colon. The association between physical activity and cancers of other sites is unclear. Potential mechanisms for the association between physical activity and reduced risk for breast and colon cancer are varied: they range from bias due to physical activity's strong correlations with other health factors (e.g., diet, smoking, alcohol use, use of medications) to the metabolic effects resulting from increased physical activity and fitness, such as reduced obesity, hormonal and reproductive effects, mechanical effects, and enhancement of the immune system. The elucidation of biologic mechanisms for an association between physical activity and cancer may provide biological support for the association. It will contribute information to determine the type, frequency, and duration of exercise needed to maximize protection. This information will be needed before large-scale community interventions are begun, in order to choose the correct interventions for the desired effect of reduced incidence of the most common cancers.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2004
Publisher: American Association for Cancer Research (AACR)
Date: 07-2008
DOI: 10.1158/1055-9965.EPI-07-2850
Abstract: Background: Estrogen is an established risk factor for breast cancer. Greater bowel motility has been associated with increased estrogen excretion and lower serum estrogen levels, suggesting that it may influence breast cancer risk. However, only one other epidemiologic study thus far, to our knowledge, has examined the relation between bowel motility and breast cancer risk. Methods: We prospectively examined whether bowel motility, measured by self-reported frequency of bowel movements, and related factors (constipation, laxative use, water consumption, and dietary fiber intake) were associated with incidence of breast cancer among 28,586 postmenopausal women, ages 50 to 76 years, in the Vitamins and Lifestyle study. Cox proportional hazards models were used to estimate multivariate-adjusted relative risks (RR) and 95% confidence intervals (95% CI). From 2000 to 2005, 507 incident invasive breast cancers among the cohort were identified. Results: Women with very frequent (≥3/d) bowel movements had a 46% decreased risk compared with 1/d women (RR, 0.54 95% CI, 0.31-0.92), but the test for linear trend was not significant (Ptrend = 0.41). Constipation was nonsignificantly associated with increased risk (RR, 1.30 for ≥1/wk versus & /y 95% CI, 0.87-1.95). No statistically significant associations were observed for the other study exposures: 10-year chemical laxative use, 10-year use of fiber laxatives, water consumption, and dietary fiber intake. Conclusion: This study adds limited support to the hypothesis that increased bowel motility lowers breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008 (7):1746–50)
Publisher: Elsevier BV
Date: 07-1995
DOI: 10.1016/0959-8049(95)00125-3
Abstract: Epidemiological, physiological and molecular models of colon carcinogenesis have been proposed. Consistent epidemiological risk factors include reduced plant-food intake (increased risk) elevated meat intake (increased risk) higher physical activity (reduced risk) and increased alcohol intake (increased risk). At the physiological level, these lifestyle variables may trigger processes that provide explanations for the associations: higher meat, fat and alcohol means more heterocyclic amines and higher levels of bile acids higher plant food means higher intake of several anticarcinogens and fibre fermentation that produces volatile fatty acids exercise has a variety of beneficial effects. This complexity is elaborated further in the context of the colonic milieu where interactions among digesta, bacteria and epithelial cells occur. The long-term likelihood of cancer is the summation of moment-to-moment changes in the colonic milieu brought about by this interaction. Possible relationships between established epidemiological risk factors, genetic susceptibility and somatic genetic changes are outlined.
Publisher: American Association for Cancer Research (AACR)
Date: 07-2008
DOI: 10.1158/1055-9965.EPI-08-0168
Abstract: Hormone therapy, estrogen plus progestin (E+P) particularly, is associated with increased risk of breast cancer. Functionally relevant polymorphisms in genes involved in sex hormone metabolism may alter exposure to exogenous sex hormones and affect risk of postmenopausal breast cancer. We evaluated associations of common polymorphisms in genes involved in estrogen and/or progesterone metabolism, E+P use, and their interactions with breast cancer risk in a case-control study of postmenopausal women (324 cases 651 controls) nested within the VITAL cohort. None of the polymorphisms studied was, by itself, statistically significantly associated with breast cancer risk. E+P use was significantly associated with increased breast cancer risk (≥10 years versus never odds ratio, 1.9 95% confidence interval, 1.3-2.8 Ptrend = 0.0002). Statistically significant interactions between CYP1A1 Ile462Val (Pinteraction = 0.04), CYP1A1 MspI (Pinteraction = 0.003), CYP1B1 Val432Leu (Pinteraction = 0.007), CYP1B1 Asn453Ser (Pinteraction = 0.04) and PGR Val660Leu (Pinteraction = 0.01), and E+P use were observed. The increased risk of breast cancer associated with E+P use was greater among women with at least one rare allele of the CYP1A1 Ile462Val, CYP1A1 MspI, CYP1B1 Asn453Ser, and PGR Val660Leu polymorphisms than among women homozygous for the common allele of these polymorphisms. Risk of breast cancer increased little with increasing years of E+P use among women with at least one CYP1B1 Val432 allele a large increase in risk was seen among women homozygous for CYP1B1 Leu432. Our results support the hypothesis that specific polymorphisms in genes involved in sex hormone metabolism may modify the effect of E+P use on breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008 (7):1751–9)
Publisher: Wiley
Date: 1996
DOI: 10.1002/(SICI)1098-2272(1996)13:2<207::AID-GEPI6>3.0.CO;2-4
Publisher: American Association for Cancer Research (AACR)
Date: 03-2006
DOI: 10.1158/1055-9965.EPI-05-0542
Abstract: Telomeres shorten with age, which may be linked to genomic instability and an increased risk of cancer. To explore this association, we analyzed telomere length in normal colorectal tissue of in iduals at different ages using quantitative-fluorescence in situ hybridization (Q-FISH) and quantitative-PCR (Q-PCR). Using Q-FISH, we also examined the histologically normal epithelium adjacent to, or distant from, colon adenomas and cancers, in addition to the neoplasms. Q-FISH and Q-PCR showed that telomere length was inversely associated with age until ∼ages 60 to 70 surprisingly, beyond this age, telomere length was positively associated with age. This association was found exclusively in epithelial, and not in stromal, cells. Peripheral blood lymphocytes showed an inverse association between telomere length and age, but without any apparent increase in telomere length in the oldest in iduals. Telomere length in larger adenoma lesions (& cm) was significantly shorter than in normal adjacent (P = 0.004) or normal distant (P = 0.05) tissue from the same in iduals. However, telomere length in histologically normal epithelium adjacent to cancers or in adenomas & cm was not statistically different from that of the normal distant mucosa or from normal controls, evidence that a telomere-shortening field effect was not present. We suggest that the positive association between telomere length and age in the oldest patients is a consequence of selective survival of elderly patients with long colonocyte telomeres. (Cancer Epidemiol Biomarkers Prev 2006 (3):573–7)
Publisher: Wiley
Date: 12-1992
DOI: 10.1111/J.1530-0277.1992.TB00704.X
Abstract: Chromatographic, peptide mapping and mass spectrometric analysis were used to examine hemoglobin (Hb) from heavy drinkers and abstainers for alcohol consumption-related modifications. Heavy drinker and abstainer hemoglobin s les contained similar amounts of glycosylated Hb and significantly different (p < 0.05) amounts of "fast" hemoglobin. The presence of higher amounts of "fast" Hb in heavy drinker relative to abstainer s les suggested the presence of alcohol-consumption related modifications. To further examine Hb for modifications, tryptic peptides of the "fast" hemoglobin HbA1c were isolated and analyzed by plasma desorption mass spectrometry (PDMS). [14C]acetaldehyde (AcH)-Hb was synthesized in vivo for use as a standard. Specific peptides were chosen based on co-migration with radiolabeled peptides from a tryptic digest of the [14C]acetaldehyde-Hb. The masses obtained by PDMS for two heavy drinker peptides were identical to two radiolabeled peptides the two pairs of peptides co-migrated on HPLC. A comparison of the observed mass for the peptides with the theoretical masses for acetaldehyde-modified Hb peptides suggested that the peptides were AcH-modified alpha and beta chain N-termini of Hb. The modified peptides were found in five of six heavy drinker s les. This is the first description of site-specific AcH-Hb adducts occurring in vivo. The routine detection of such adducts has potential for characterizing usual alcohol intake.
Publisher: Oxford University Press (OUP)
Date: 20-11-2015
DOI: 10.1093/AJE/KWV133
Publisher: American Association for Cancer Research (AACR)
Date: 05-2011
DOI: 10.1158/1055-9965.EPI-10-0675
Abstract: Background: Genome-wide association studies (GWAS) have led to the identification of a number of common susceptibility loci for colorectal cancer (CRC) however, none of these GWAS have considered gene–environment (G × E) interactions. Therefore, it is unclear whether current hits are modified by environmental exposures or whether there are additional hits whose effects are dependent on environmental exposures. Methods: We conducted a systematic search for G × E interactions using genome wide data from the Colon Cancer Family Registry that included 1,191 cases of microsatellite stable (MSS) or microsatellite instability–low (MSI-L) CRC and 999 controls genotyped using either the Illumina Human1M or Human1M-Duo BeadChip. We tested for interactions between genotypes and 14 environmental factors using 3 methods: a traditional case–control test, a case-only test, and the recently proposed 2-step method by Murcray and colleagues. All potentially significant findings were replicated in the ARCTIC Study. Results: No G × E interactions were identified that reached genome-wide significance by any of the 3 methods. When analyzing previously reported susceptibility loci, 7 significant G × E interactions were found at a 5% significance level. We investigated these 7 interactions in an independent s le and none of the interactions were replicated. Conclusions: Identifying G × E interactions will present challenges in a GWAS setting. Our power calculations illustrate the need for larger s le sizes however, as CRC is a heterogeneous disease, a tradeoff between increasing s le size and heterogeneity needs to be considered. Impact: The results from this first genome-wide analysis of G × E in CRC identify several challenges, which may be addressed by large consortium efforts. Cancer Epidemiol Biomarkers Prev 20(5) 758–66. ©2011 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/0008-5472.23814635
Abstract: Selected characteristics of the participants.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 17-10-2012
DOI: 10.1126/SCITRANSLMED.3004956
Abstract: Natural product shows remarkable activity against pancreatic ductal adenocarcinoma across preclinical model systems.
Publisher: Elsevier BV
Date: 07-2007
Publisher: American Association for Cancer Research (AACR)
Date: 10-2020
DOI: 10.1158/1055-9965.EPI-20-0525
Abstract: Prevalence of Helicobacter pylori (H. pylori) infection, the main risk factor for gastric cancer, has been decreasing in the United States however, there remains a substantial racial disparity. Moreover, the time-trends for prevalence of CagA-positive H. pylori infection, the most virulent form, are unknown in the U.S. population. We sought to assess prevalence of CagA-positive H. pylori infection over time by race in the United States. We utilized multiplex serology to quantify antibody responses to H. pylori antigens in 4,476 participants across five cohorts that s led adults from 1985 to 2009. Using log-binomial regression models, we calculated prevalence ratios and 95% confidence intervals for the association between H. pylori–CagA sero-prevalence and birth year by race. African Americans were three times more likely to be H. pylori–CagA sero-positive than Whites. After adjustment, H. pylori–CagA sero-prevalence was lower with increasing birth year among Whites (Ptrend = 0.001), but remained stable for African Americans. When stratified by sex and education separately, the decline in H. pylori–CagA sero-positivity among Whites remained only for females (Ptrend & 0.001) and was independent of educational attainment. Among African Americans, there was no difference by sex furthermore, sero-prevalence increased with increasing birth year among those with a high school education or less (P = 0.006). Among in iduals in the United States born from the 1920s to 1960s, H. pylori–CagA sero-prevalence has declined among Whites, but not among African Americans. Our findings suggest a widening racial disparity in the prevalence of the most virulent form of H. pylori, the main cause of gastric cancer.
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: The association between body mass index (BMI) and colon cancer has been reported to be different for men and women. No prior literature has examined if estrogen influences these differences. Using data from an incident population-based case (n = 1,972) and control (n = 2386) study of colon cancer we evaluated if estrogen modifies the association between BMI and risk of colon cancer. Women who were estrogen-negative (postmenopausal women not taking hormone replacement therapy, HRT) were at increased risk of colon cancer regardless of indicator of estrogen status used (i.e. estrogen-negative compared to estrogen-positive women defined as either being premenopausal or postmenopausal women using HRT, OR 1.54, 95% CI 1.23-1.93 no recent exposure to estrogens compared to current or HRT use within the past 2 years, OR 1.58, 95% CI 1.24-2.00 postmenopausal women not currently using HRT compared to postmenopausal women taking HRT, OR 1.65, 95% CI 1.29-2.12). BMI (kg/m2) was not associated with an increased risk of colon cancer among women who were estrogen-negative. However, women who were estrogen-positive experienced a greater than two-fold increase in colon cancer risk if they had a BMI of > 30 relative to those who had a BMI of <23 (for estrogen-positive, OR, 2.50, 95% CI 1.51-4.13 premenopausal, OR 2.19, 95% CI 0.94-5.07 postmenopausal using HRT, OR 3.36, 95% CI 1.58-7.13). Among men the colon cancer risk associated with BMI decreased with advancing age. Physical activity modified the increased colon cancer risk associated with a large BMI. These data suggest the importance of estrogen in colon cancer etiology. Being estrogen-negative resulted in a significant increased risk of colon cancer. However, BMI significantly increased the risk of colon cancer among women who were estrogen-positive. We hypothesize that estrogen up-regulates IGF-I receptors and IRS-I levels in the colon, which in turn increases susceptibility to obesity-induced increased levels of insulin. We further hypothesize that androgens may have similar effects in men given the decline in colon cancer risk associated with BMI with advancing age.
Publisher: American Association for Cancer Research (AACR)
Date: 07-2010
DOI: 10.1158/1055-9965.EPI-10-0318
Abstract: Background: Use of nonvitamin, nonmineral “specialty” supplements has increased substantially over recent decades. Several supplements may have anti-inflammatory or anticancer properties. Additionally, supplements taken for symptoms of menopause have been associated with reduced risk of breast cancer in two case-control studies. However, there have been no prospective studies of the association between the long-term use of these supplements and breast cancer risk. Methods: Participants were female members of the VITamins And Lifestyle (VITAL) Cohort. Postmenopausal women, ages 50 to 76 years, who were residents of western Washington State, completed a 24-page baseline questionnaire in 2000 to 2002 (n = 35,016). Participants were queried on their recency (current versus past), frequency (days/week), and duration (years) of specialty supplement use. Incident invasive breast cancers (n = 880) from 2000 to 2007 were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariable-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Results: Current use of fish oil was associated with reduced risk of breast cancer (HR, 0.68 95% CI, 0.50-0.92). Ten-year average use was suggestive of reduced risk (P trend = 0.09). These results held for ductal but not lobular cancers. The remaining specialty supplements were not associated with breast cancer risk: Specifically, use of supplements sometimes taken for menopausal symptoms (black cohosh, dong quai, soy, or St. John's wort) was not associated with risk. Conclusions: Fish oil may be inversely associated with breast cancer risk. Impact: Fish oil is a potential candidate for chemoprevention studies. Until that time, it is not recommended for in idual use for breast cancer prevention. Cancer Epidemiol Biomarkers Prev 19(7) 1696–708. ©2010 AACR.
Publisher: Springer Science and Business Media LLC
Date: 08-06-2012
Publisher: American Association for Cancer Research (AACR)
Date: 10-2018
DOI: 10.1158/1055-9965.EPI-18-0249
Abstract: Background: Antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG) proteins, especially pilus protein Gallo2178, have been consistently associated with colorectal cancer risk. Previous case–control studies and prospective studies with up to 8 years of follow-up, however, were unable to decipher the temporality of antibody responses to SGG in the context of the long-term multistep development of colorectal cancer. In this study, we analyzed a large U.S. colorectal cancer cohort consortium with follow-up beyond 10 years for antibody responses to SGG. Methods: We applied multiplex serology to measure antibody responses to 9 SGG proteins in participants of 10 prospective U.S. cohorts (CLUE, CPSII, HPFS, MEC, NHS, NYUWHS, PHS, PLCO, SCCS, and WHI) including 4,063 incident colorectal cancer cases and 4,063 matched controls. Conditional logistic regression was used to assess whether antibody responses to SGG were associated with colorectal cancer risk, overall and by time between blood draw and diagnosis. Results: Colorectal cancer risk was increased among those with antibody responses to Gallo2178, albeit not statistically significant [OR, 1.23 95% confidence interval (CI), 0.99–1.52]. This association was stronger for cases diagnosed & years after blood draw (OR, 1.40 95% CI, 1.09–1.79), but was not found among cases diagnosed ≥10 years after blood draw (OR, 0.79 95% CI, 0.50–1.24). Conclusions: In a large cohort consortium, we reproduced the association of antibody responses to SGG Gallo2178 with colorectal cancer risk for in iduals diagnosed within 10 years after blood draw. Impact: This timing-specific finding suggests that antibody responses to SGG are associated with increased colorectal cancer risk only after tumorigenesis has begun. Cancer Epidemiol Biomarkers Prev 27(10) 1186–94. ©2018 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/0008-5472.23814632
Abstract: Summary of G × BMI analyses using 1DF, two-step, and 3DF analyses.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2014
DOI: 10.1038/BJC.2014.66
Publisher: Wiley
Date: 2000
DOI: 10.1002/1097-0215(20000901)87:5<728::AID-IJC16>3.0.CO;2-G
Publisher: American Association for Cancer Research (AACR)
Date: 06-2005
DOI: 10.1158/1055-9965.EPI-04-0920
Abstract: Objective: Hormone therapy use has been positively associated with mammographic density in several studies. However, few studies have examined the association between endogenous hormone levels and mammographic density. Therefore, we evaluated the relationship of endogenous sex hormones, insulin-like growth factor (IGF), and lipids with mammographic density in 88 overweight, postmenopausal women not taking hormone therapy. Methods: Percent density and dense area were evaluated as continuous measures using a computer-assisted program. We used multiple linear regression to evaluate the associations of sex hormones, IGF, and cholesterol with mammographic density, adjusting for confounders, including adiposity. We evaluated stratification by history of hormone therapy use (former versus never) and hormone therapy latency (& versus ≥5 years). Results: Among former hormone therapy users, mammographic density was inversely associated with circulating levels of estrone (P = 0.01), estradiol (P = 0.003), free estradiol (P = 0.004), testosterone (P = 0.04), free testosterone (P = 0.02), androstenedione (P & 0.001), dehydroepiandrosterone (P = 0.01), and the ratio of IGF-I to its binding protein (IGF-I/IGFBP-3 P = 0.04). We found similar associations when we limited the analyses to women who had used hormone therapy within the past 5 years. We also noted positive associations of mammographic density with total cholesterol (P = 0.03) and low-density lipoprotein (P = 0.03) among former hormone therapy users. No associations were noted among women who had never used hormone therapy. Conclusions: These results suggest that there is an inverse relationship between endogenous sex hormones and mammographic density in postmenopausal women among former users of hormone therapy. This is not consistent with the hormone therapy literature and should be confirmed in larger studies.
Publisher: Oxford University Press (OUP)
Date: 12-06-2015
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.BBMT.2006.05.016
Abstract: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) play key roles in intracellular folate metabolism. Polymorphisms in these enzymes have been shown to modify toxicity of methotrexate (MTX) after hematopoietic cell transplantation. In this study, we evaluated the risk of acute graft-versus-host disease (GVHD) associated with genetic variation in recipient and donor MTHFR and TS genotypes to assess whether genotype alters the efficacy of MTX in acute GVHD prophylaxis. Data on the transplantation course were abstracted from medical records for 304 adults who received allogeneic hematopoietic cell transplants. MTHFR (C677T and A1298C) and TS (enhancer-region 28-base pair repeat, TSER, and 1494del6) genotypes were determined using polymerase chain reaction/restriction fragment length polymorphism and TaqMan assays. Multivariable logistic regression was used to assess the associations between genotypes and risk of acute GVHD. Compared with recipients with the wild-type MTHFR 677CC genotype, those with the variant 677T allele showed a decreased risk of detectable acute GVHD (677CT: odds ratio, 0.8 95% confidence interval, 0.4-1.6 677TT: odds ratio, 0.4 95% confidence interval, 0.2-0.8 P for trend = .01). The variant MTHFR 1298C allele in recipients was associated with an increased risk of acute GVHD compared with the wild-type MTHFR 1298AA genotype (1298AC: odds ratio, 2.0 95% confidence interval, 1.1-3.9 1298CC: odds ratio, 3.6 95% confidence interval, 1.0-12.7 P for trend < .01). No association with risk of acute GVHD was observed for donor MTHFR genotypes or for recipient or donor TS genotypes, with the exception of an increase in acute GVHD among recipients whose donors had the TSER 3R/2R genotype (odds ratio, 3.0 95% confidence interval, 1.3-7.2). These findings indicate that host, but not donor, MTHFR genotypes modify the risk of acute GVHD in recipients receiving MTX, in a manner consistent with our previously reported associations between MTHFR genotypes and MTX toxicity. A direct trade-off between drug toxicity and drug efficacy may play a role. Alternatively, the systemic folate environment, regulated by host tissues, might influence donor T-cell growth and activity.
Publisher: Wiley
Date: 15-10-1996
DOI: 10.1002/(SICI)1097-0142(19961015)78:8<1666::AID-CNCR5>3.0.CO;2-C
Abstract: Site of the carcinoma within the colon in relation to age and sex may provide clues into the etiology of the disease. Incidence of colon carcinoma by age, sex, and tumor site at a population-based level are reported infrequently. The goal of this study was to describe the distribution of colon carcinoma (excluding cancers of the rectosigmoid junction and rectum) by age at diagnosis, sex, and site of the tumor within the colon. These factors were also evaluated in conjunction with disease stage at the time of diagnosis. Data from three geographically distinct populations were used to describe rates of colon carcinoma and the distribution of tumors by age, tumor site, and stage at diagnosis. All colon carcinoma cases diagnosed within a 3-year period within the areas are included. Approximately 50% of all cancers in men and greater than 50% of cancers in women were in the proximal segment of the colon. Men who were diagnosed prior to age 50 and both men and women diagnosed at age 70 or older had predominantly proximal cancers. People with proximal cancers and people diagnosed prior to age 50 were more likely to have more advanced disease. Both men and women have more proximal cancers with advancing age, which are associated with more advanced disease. Observed trends in cancer site distributions could reflect screening practices, environmental and genetic factors, or a combination of these variables.
Publisher: BMJ
Date: 10-2013
DOI: 10.1136/BMJ.F5446
Publisher: American Association for Cancer Research (AACR)
Date: 08-2010
DOI: 10.1158/1055-9965.EPI-09-1097
Abstract: Background: Supplement use among cancer patients is high, and folic acid intake in particular may adversely affect the progression of colorectal cancer. Few studies have evaluated the use of folic acid–containing supplements (FAS) and its predictors in colorectal cancer patients. Objective: To assess the use of FAS, change in use, and its predictors after colorectal cancer diagnosis. Design: We used logistic regression models to investigate predictors of FAS use and its initiation after colorectal cancer diagnosis in 1,092 patients recruited through the Colon Cancer Family Registry. Results: The prevalence of FAS use was 35.4% before and 55.1% after colorectal cancer diagnosis (P = 0.004). Women were more likely than men to use FAS after diagnosis [odds ratio (OR), 1.47 95% confidence interval (95% CI), 1.14-1.89], as were those consuming more fruit (Ptrend & 0.0001) or vegetables (Ptrend = 0.001), and U.S. residents (P & 0.0001). Less likely to use FAS after diagnosis were nonwhite patients (OR, 0.66 95% CI, 0.45-0.97), current smokers (OR, 0.67 95% CI, 0.46-0.96), and those with higher meat intake (Ptrend = 0.03). Predictors of FAS initiation after diagnosis were generally similar to those of FAS use after diagnosis, although associations with race and vegetable intake were weaker and those with exercise stronger. Conclusions: Our analysis showed substantial increases in the use of FAS after diagnosis with colorectal cancer, with use or initiation more likely among women, Caucasians, U.S. residents, and those with a health-promoting life-style. Impact: Studies of cancer prognosis that rely on prediagnostic exposure information may result in substantial misclassification. Cancer Epidemiol Biomarkers Prev 19(8) 2023–34. ©2010 AACR.
Publisher: Wiley
Date: 16-05-1997
DOI: 10.1002/(SICI)1097-0215(19970516)71:4<706::AID-IJC32>3.0.CO;2-6
Publisher: Oxford University Press (OUP)
Date: 18-01-2007
Abstract: Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Metabolism of omega-6 (n-6) PUFAs results in the production of pro-inflammatory mediators whereas downstream products of omega-3 (n-3) PUFAs have lower inflammatory activity. Elevated n-3 PUFA intake from dietary fish may be associated with lower risk of colorectal neoplasia among those with genetic variants resulting in higher levels of pro-inflammatory mediators. We investigated interactions between dietary fish intake and polymorphisms in cyclooxygenase (COX)-1, COX-2, ALOX5 and PGIS in a case-control study of adenomas (N = 522), hyperplastic polyps (N = 194) and polyp-free controls (N = 626). Polyp risk did not differ by fish intake. A suggested interaction with fish intake was observed for COX-1 P17L. Among those who were homozygous wild type, increasing fish intake was associated with a modestly reduced risk of adenoma, whereas among those with at least one variant allele, the reverse trend was observed (p-interaction = 0.08). The interaction was statistically significant when non-steroidal anti-inflammatory drug (NSAID) use was also taken into account: among those with COX-1 17PP genotypes, high fish intake and regular NSAID use was associated with a decreased risk compared with low fish intake and low NSAID use (odds ratio = 0.60, 95% confidence interval 0.33-1.09). The opposite association was observed among those with COX-1 17PL or LL genotypes (p-interaction = 0.04). Our results suggest that the effects of dietary n-3 PUFA intake and NSAID use may differ by genetic variation in COX-1.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/0008-5472.23814641
Abstract: supplementary materials
Publisher: American Association for Cancer Research (AACR)
Date: 15-04-2004
DOI: 10.1158/0008-5472.CAN-03-3393
Abstract: Elevated circulating estrogens and a sedentary lifestyle increase risk for breast cancer. The effect of exercise on circulating estrogens in sedentary postmenopausal women is unknown. The objective of this study was to examine the effects of a 12-month moderate-intensity exercise intervention on serum estrogens. We randomly assigned 173 sedentary, overweight (body mass index & 24.0 kg/m2, body fat & 33%), postmenopausal women, ages 50–75 years, not using hormone therapy, living in the Seattle, Washington, area for the next year, and willing to be randomly assigned to an exercise intervention or stretching control group. The exercise intervention included facility and home-based exercise (45 min, 5 days/week moderate intensity sports/recreational exercise). A total of 170 (98.3%) women completed the study with exercisers averaging 171 min/week of exercise. After 3 months, exercisers experienced declines in estrone, estradiol, and free estradiol of 3.8, 7.7, and 8.2%, respectively, versus no change or increased concentrations in controls (P = 0.03, 0.07, and 0.02, respectively). At 12 months, the direction of effect remained the same, although the differences were no longer statistically significant. The effect was limited to women who lost body fat: women whose percentage of body fat [by dual energy x-ray absortiometry (DEXA)] decreased by ≥2% had statistically significant (comparing exercisers versus controls) decreases at 12 months of 11.9, 13.7, and 16.7% for serum estrone, estradiol, and free estradiol, respectively. We concluded that a 12-month moderate-intensity exercise intervention in postmenopausal women resulted in significant decreases in serum estrogens. The association between increased physical activity and reduced risk for postmenopausal breast cancer may be partly explained by effects on serum estrogens.
Publisher: Springer Science and Business Media LLC
Date: 1997
Abstract: Hormonal factors have been inconsistently associated with colon cancer risk in women. The associations between reproductive events, menstrual factors, exogenous hormones, and colon cancer were evaluated in a large case-control study (894 female cases and 1,120 female age-matched population-based controls) in the United States, stratifying by age at diagnosis, tumor site, family history and other potential risk factors. Overall, higher parity was associated with a marginally decreased risk of colon cancer (five or more births compared with nulliparous: odds ratio [OR] = 0.75, 95 percent confidence interval [CI] = 0.53-1.06) after adjusting for age at diagnosis, family history of colorectal cancer, vigorous lifetime physical activity, body mass index (BMI) (wt/ht1.5), total energy intake, and aspirin use. No important associations were observed for other reproductive or menstrual events. An inverse association between recent use of hormone replacement therapy (HRT) and colon cancer was observed (OR = 0.71, CI = 0.56-0.89). Although interaction terms were not significant, this inverse association appeared to be more pronounced for those with an older age at diagnosis for those without a first-degree relative with colorectal cancer and for those with a relatively low BMI. The reduced risk associated with HRT use did not appear to be explained by other behaviors related to HRT use.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2012
DOI: 10.1038/AJG.2012.21
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426033.V1
Abstract: Supplementary Table S2
Publisher: American Association for Cancer Research (AACR)
Date: 24-02-2022
DOI: 10.1158/1055-9965.EPI-21-1003
Abstract: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. In idual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (& g/day) with light-to-moderate drinkers (1–28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 & 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose–response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11 95% confidence interval (CI), 1.06–1.17 OR for AA genotype = 1.22 95% CI, 1.14–1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. The study identifies multifaceted evidence of a possible functional effect for rs1318920.
Publisher: American Medical Association (AMA)
Date: 23-09-1992
Publisher: Wiley
Date: 03-2003
Abstract: We present a method of data reduction using a wavelet transform in discriminant analysis when the number of variables is much greater than the number of observations. The method is illustrated with a prostate cancer study, where the s le size is 248, and the number of variables is 48,538 (generated using the ProteinChip technology). Using a discrete wavelet transform, the 48,538 data points are represented by 1271 wavelet coefficients. Information criteria identified 11 of the 1271 wavelet coefficients with the highest discriminatory power. The linear classifier with the 11 wavelet coefficients detected prostate cancer in a separate test set with a sensitivity of 97% and specificity of 100%.
Publisher: Springer Science and Business Media LLC
Date: 06-06-2022
DOI: 10.1038/S41467-022-30916-1
Abstract: Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87–100%)). All monoallelic MUTYH carriers are classified with the non- MUTYH carriers. The classifier provides evidence for a pathogenic classification for two VUS and a benign classification for five VUS. Somatic hotspot mutations KRAS p.G12C and PIK3CA p.Q546K are associated with colorectal cancers from biallelic MUTYH carriers compared with non-carriers ( p = 2 × 10 −23 and p = 6 × 10 −11 , respectively). Here, we demonstrate the potential application of mutational signatures to tumor sequencing workflows to improve the identification of biallelic MUTYH carriers.
Publisher: Springer Science and Business Media LLC
Date: 27-12-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1997
DOI: 10.1097/00043426-199705000-00007
Abstract: Due to the use of combined modalities of multiagent chemotherapy, radiation therapy, and surgery, many children with a diagnosis of cancer are now surviving into adulthood. This pilot study sought to determine the feasibility of establishing a cohort of childhood cancer survivors and then to develop methods to trace and contact eligible participants. A retrospective cohort design was used. Four hundred and forty subjects who were treated for cancer at the University of Minnesota Hospital before the age of 21, between 1970 and 1986, had survived 5 years, and were alive at last contact were eligible. Tracing efforts were undertaken if the address was more than 2 years old or if a letter was returned by the post office. Contact procedures in this study were designed to determine whether participation rates differed according to the method of contact. In this cohort of 440 in iduals, 11 had died and were not traced. Of the remaining 429 eligible in iduals, 408 (95.1%) were successfully contacted. Successful tracing efforts differed by both current age and age at diagnosis. Once contacted, 370 (90.6%) agreed to participate in this study and returned a baseline health questionnaire. Each method of participation, and the combination of methods, showed similar percentages of participation. Results from this pilot study show that appropriate methods exist to establish a cohort of adults who have not been contacted since childhood.
Publisher: Oxford University Press (OUP)
Date: 08-2015
DOI: 10.1093/JNCI/DJV210
Publisher: Springer Science and Business Media LLC
Date: 1999
Abstract: Hormone replacement therapy (HRT) has been inversely associated with colon cancer incidence in several epidemiologic studies. In this study we used data from a population-based incident case-control study of colon cancer to evaluate the role of HRT use in survival after diagnosis with colon cancer. Data from 815 postmenopausal women living in Utah, California, and Minnesota diagnosed between 1 September 1991 and 30 September 1994 were used to examine associations between HRT and survival. After adjusting for age at time of diagnosis, stage of disease at time of diagnosis, study center, and body mass index (BMI), we observed that women who had ever used HRT had a 30% lesser probability of dying of any cause and a 40% lower probability of dying from colon cancer specifically during the follow-up period. Further evaluation by years of HRT use showed that those who had used HRT for 4 or more years had the lowest risk of dying of colon cancer (hazard rate ratio 0.5, 95% confidence interval 0.3-0.9). Evaluation of other lifestyle variables with HRT use did not show significant confounding or effect modification. These findings suggest that HRT use may improve short-term survival after diagnosis with colon cancer there is no suggestion that HRT use is detrimental to survival.
Publisher: American Association for Cancer Research (AACR)
Date: 10-2013
DOI: 10.1158/1055-9965.EPI-13-0518
Abstract: Genetic association studies have identified more than a dozen genes associated with risk of pancreatic cancer. Given this genetic heterogeneity, family history can be useful for identifying in iduals at high risk for this disease. The goal of this analysis was to evaluate associations of family history of diabetes and family history of pancreatic cancer with risk of pancreatic cancer. PACIFIC is a case–control study based on two large health plans. Cases were diagnosed with pancreatic ductal adenocarcinoma (PDA) and controls were selected from the health plan enrollment databases and frequency matched to cases. Family history data were collected using an interviewer-administered questionnaire and were available on 654 cases and 697 controls. Logistic regression was used for the association analyses. First-degree relative history of diabetes was statistically significantly associated with increased risk of PDA [OR, 1.37 95% confidence interval (CI), 1.10–1.71]. The highest risk of PDA was observed for an offspring with diabetes (OR, 1.95 95% CI, 1.23–3.09). In addition, history of pancreatic cancer increased risk for PDA with an OR of 2.79 (95% CI, 1.44–4.08) for any first-degree relative history of pancreatic cancer. This population-based analysis showed that family history of diabetes was associated with increased risk of PDA and confirmed previous studies showing that first-degree family history of pancreatic cancer is associated with PDA. These results support the need for ongoing studies of genetic influences on pancreatic cancer in large s les and investigations of possible pleiotropic genetic effects on diabetes and pancreatic cancer. Cancer Epidemiol Biomarkers Prev 22(10) 1913–7. ©2013 AACR.
Publisher: Oxford University Press
Date: 06-03-2009
Publisher: Wiley
Date: 03-1998
DOI: 10.1002/(SICI)1099-1557(199803/04)7:2<99::AID-PDS320>3.0.CO;2-0
Publisher: Oxford University Press (OUP)
Date: 1979
DOI: 10.1093/IJE/8.2.137
Abstract: Thyroid status is known to have an important bearing on the ability of a woman to conceive, and to bring a normal infant to term. Thyroid status has changed in a number of previously iodine deficient countries as a result of recent iodization programmes. In this study, examination has been made of changes in the rates of two pregnancy outcomes in Tasmania, a State of Australia, namely, stillbirth and infant death due to congenital anomalies. Tasmania began iodine supplementation in 1950. Stillbirth rates declined more rapidly than in Australia as a whole, but show a peak associated with the peak of iodine-induced thyrotoxicosis in 1966. Congenital anomalies causing death show an initial rise in the early 1950s. It is suggested that this is due to persistence of iodine deficiency in the foetus after maternal iodine status improved sufficiently to allow term delivery of a live infant. The later fall coincides with the reaching of reproductive age by the first cohort of Tasmanian women who had been iodine sufficient since childhood, who would therefore not deprive their own foetus of iodine. Examination of trends in New Zealand, Switzerland and Finland, which have each introduced iodization programmes, confirms the largely beneficial effect of iodine supplementation on the rate of infant death due to congenital anomalies.
Publisher: Springer Science and Business Media LLC
Date: 21-09-2013
Publisher: Wiley
Date: 25-06-2010
DOI: 10.1002/GEPI.20494
Publisher: Public Library of Science (PLoS)
Date: 22-04-2014
Publisher: American Association for Cancer Research (AACR)
Date: 08-2005
Publisher: CMA Joule Inc.
Date: 26-04-2010
DOI: 10.1503/CMAJ.091540
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426033
Abstract: Supplementary Table S2
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426036
Abstract: Supplementary Table S1
Publisher: Public Library of Science (PLoS)
Date: 17-04-2014
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426030
Abstract: Supplementary Table S3
Publisher: Wiley
Date: 09-11-2006
DOI: 10.1002/IJC.22342
Abstract: It has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population-based case-control study of incident colon cancer were used to evaluate whether intake of dietary, obesity, physical activity and nonsteroidal antiinflammatory drugs are associated with a CpG island methylator phenotype (CIMP). The BRAF V600E mutation and 5 CpG island markers (MINT1, MINT2, MINT31, p16 and hMLH1) were assessed in 1154 cases of colon cancer. We hypothesized that dietary factors involved in DNA methylation, cruciferous vegetables and use of aspirin/NSAIDs would be associated with CIMP-high tumors. Dietary folate, vitamins B(6) and B(12), methionine and alcohol were not associated with increased likelihood of colon tumors with the CIMP-high (2 or more markers methylated) phenotype. Dietary fiber, physical activity and aspirin and other nonsteroidal antiinflammatory drugs were inversely associated with both CIMP-low and CIMP-high tumors. Our results also suggested non-CIMP pathways as well. Obese in iduals were at 2-fold increased risk of having a CIMP-low tumor. Alcohol was associated with an increased risk of tumors that were MSI+ and CIMP-low. In the presence of smoking 20 or more cigarettes per day, use of NSAIDs did not protect against a BRAF mutation. Our data suggest multiple pathways to colon cancer. They do not support a unique role for dietary folate, alcohol, vitamins B(6) and B(12) and methionine in a CpG island methylator phenotype.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2011
Publisher: Massachusetts Medical Society
Date: 31-08-2006
DOI: 10.1056/NEJME068158
Publisher: Public Library of Science (PLoS)
Date: 13-10-2010
Publisher: Oxford University Press (OUP)
Date: 1991
DOI: 10.1093/IJE/20.1.151
Abstract: The associations of body mass and body fat distribution, as measured by waist-to-hip circumference ratio, with serum concentrations of sex hormones and sex hormone binding globulin were examined in 88 postmenopausal women. Body mass index (BMI) was significantly and negatively associated with sex hormone binding globulin (SHBG) (r = -0.41), luteinizing hormone (LH) (r = -0.40) and follicle stimulating hormone (FSH) (r = -0.38) and was also significantly positively associated with both total and free oestradiol (r = 0.40 and 0.45, respectively). Waist-to-hip circumference ratio was significantly negatively correlated with SHBG (r = -0.53), LH (r = -0.35), and FSH (r = -0.35). After adjustment for BMI and other related factors, waist-to-hip circumference ratio was significantly and negatively associated with SHBG, LH, and FSH, and demonstrated a significant curvilinear relationship with free testosterone. These results suggest that in postmenopausal women, abdominal adiposity is associated with a relatively more androgenic sex hormone profile.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22420548.V1
Abstract: Table S2 shows no significant differences were observed between regular use of NSAIDs and CRC risk across cancer subsites or stages.
Publisher: Elsevier BV
Date: 11-1992
DOI: 10.1016/0741-8329(92)90098-U
Abstract: The formation of stable hemoglobin adducts was examined (in the absence of an added reducing agent) in metabolizing red blood cells (RBCs) exposed to micromolar concentrations of acetaldehyde for up to 48 hours in vitro. The rapid disappearance of acetaldehyde due to oxidation by RBC aldehyde dehydrogenase was prevented by pretreating the cells with the inhibitor cyanamide. The RBCs remained viable for 48 hours (37 degrees C) as determined by cell hemolysis and glycolytic activity. [14C]acetaldehyde-modified hemoglobin was assessed in untreated and in cyanamide-pretreated cells. In untreated cells, after 3 hours of exposure to 50 and 200 nmol/ml of [14C]acetaldehyde, the molar ratios of acetaldehyde to hemoglobin were 0.00069 and 0.0038, respectively [14C]acetaldehyde concentrations decreased to less than 4% of the initial levels within 3 hours. In cyanamide-pretreated RBCs, the molar ratios of acetaldehyde bound to hemoglobin ranged from 0.0013 after 3 hours of exposure to 20 nmol/ml [14C]acetaldehyde up to 0.039 after 48 hours of exposure to 200 nmol/ml [14C]acetaldehyde. Following tryptic digestion of [14C]acetaldehyde-hemoglobin and separation of peptides by high-performance liquid chromatography, significant incorporation of [14C]acetaldehyde was observed in nine peptides. Modifications of the labeled peptides remain to be characterized.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2013
DOI: 10.1158/1055-9965.EPI-13-0409
Abstract: Background: Both shorter and longer telomeres in peripheral blood leukocyte (PBL) DNA have been associated with cancer risk. However, associations remain inconsistent across studies of the same cancer type. This study compares DNA preparation methods to determine telomere length from patients with colorectal cancer. Methods: We examined PBL relative telomere length (RTL) measured by quantitative PCR (qPCR) in 1,033 patients with colorectal cancer and 2,952 healthy controls. DNA was extracted with phenol/chloroform, PureGene, or QIA . Results: We observed differences in RTL depending on DNA extraction method (P & 0.001). Phenol/chloroform-extracted DNA had a mean RTL (T/S ratio) of 0.78 (range 0.01–6.54) compared with PureGene-extracted DNA (mean RTL of 0.75 range 0.00–12.33). DNA extracted by QIA yielded a mean RTL of 0.38 (range 0.02–3.69). We subsequently compared RTL measured by qPCR from an independent set of 20 colorectal cancer cases and 24 normal controls in PBL DNA extracted by each of the three extraction methods. The range of RTL measured by qPCR from QIA -extracted DNA (0.17–0.58) was less than from either PureGene or phenol/chloroform (ranges, 0.04–2.67 and 0.32–2.81, respectively). Conclusions: RTL measured by qPCR from QIA -extracted DNA was less than from either PureGene or phenol/chloroform (P & 0.001). Impact: Differences in DNA extraction method may contribute to the discrepancies between studies seeking to find an association between the risk of cancer or other diseases and RTL. Cancer Epidemiol Biomarkers Prev 22(11) 2047–54. ©2013 AACR.
Publisher: Informa UK Limited
Date: 05-2011
Publisher: Springer Science and Business Media LLC
Date: 11-04-2011
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/0008-5472.23814635.V1
Abstract: Selected characteristics of the participants.
Publisher: Elsevier BV
Date: 07-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2006
Publisher: Springer Science and Business Media LLC
Date: 12-2003
DOI: 10.1023/B:CACO.0000007970.04094.76
Abstract: Colorectal cancer is the second leading cause of cancer death among US men and women. A number of studies report that hormone replacement therapy (HRT) reduces the risk of colorectal cancer, but fewer studies have examined the relation between HRT use and survival after diagnosis and none examined this relation by anatomic location of the primary colon tumor. Data from a cohort of 699 women 50-79 years of age diagnosed with colon cancer between 1980 and 1998 in a large Health Maintenance Organization based in Seattle, Washington were analyzed to examine the relation between HRT use prior to diagnosis and survival. Use of HRT was ascertained from a computerized pharmacy database. HRT use was associated with a 41% reduction in risk of death after adjustment for age, stage, and diagnosis year (p= 0.037). The association between HRT use and colon cancer survival was strongest among women with cancer in the distal colon (hazard rate ratio 0.33, 95% confidence interval, 95% CI: 0.13-0.83), while little or no association between HRT use and survival was observed among women with proximal tumors (HRR 0.78, 95% CI: 0.42-1.44). These findings suggest that HRT use is associated with improved survival from colon cancer. Future observational and laboratory studies should shed light on how hormones may be related to reduced incidence and improved prognosis.
Publisher: American Association for Cancer Research (AACR)
Date: 02-2014
DOI: 10.1158/1055-9965.EPI-13-0780
Abstract: Cigarette smoking (CS), hormone therapy (HT), and folate intake (FI) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. The TP53 (p53) protein, encoded by the TP53 tumor-suppressor gene that is commonly mutated in colorectal cancer, can be readily assessed to differentiate biologically distinct colorectal cancer subtypes. In this prospective cohort study, we examined CS-, HT-, and FI-associated colorectal cancer risks by TP53 protein expression level among Iowa Women's Health Study (IWHS) participants. The IWHS recruited 41,836 randomly selected Iowa women, ages 55 to 69 years, with a valid driver's license at study entry in 1986. Self-reported exposure variables were assessed at baseline. Incident colorectal cancer cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected and evaluated for TP53 protein expression by immunohistochemistry. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between CS, HT, or FI and TP53-defined colorectal cancer subtypes. Informative environmental exposure and protein expression data were available for 492 incident colorectal cancer cases: 222 (45.1%) TP53 negative, 72 (14.6%) TP53 low, and 198 (40.2%) TP53 high. Longer duration (& years) of HT was inversely associated with TP53 high colorectal cancers (RR, 0.50 95% CI, 0.27–0.94). No other statistically significant associations were observed. These data support possible heterogeneous effects from HT on TP53-related pathways of colorectal carcinogenesis in older women. Cancer Epidemiol Biomarkers Prev 23(2) 350–5. ©2013 AACR.
Publisher: Oxford University Press (OUP)
Date: 11-03-2014
Abstract: Chemoprevention is proposed as a clinical analogue of population prevention, aimed at reducing likelihood of disease progression, not across the population, but in identified high-risk in iduals and not by behavioral or lifestyle modification, but by the use of pharmaceutical agents. Cardiovascular chemoprevention is successful via control of hyperlipidemias and hypertension. However, chemoprevention of cancer is an almost universal failure: not only are some results null even more frequently, there is an excess of disease, including disease that the agents were chosen specifically to reduce. A brief introduction is followed by the evidence for a wide variety of agents and their largely deleterious, sometimes null, and in one case, largely beneficial, consequences as possible chemopreventives. The agents include (i) those that are food derived and their synthetic analogues: β-carotene, folic acid, retinol and retinoids, vitamin E, multivitamin supplements, vitamin C, calcium and selenium and (ii) agents targeted at metabolic and hormonal pathways: statins, estrogen and antagonists, 5α-reductase inhibitors. There are two agents for which there is good evidence of benefit when the strategy is focused on those at defined high risk but where wider application is much more problematic: aspirin and tamoxifen. The major problems with cancer chemoprevention are presented. This is followed by a hypothesis to explain the failure of cancer chemoprevention as an enterprise, arguing that the central tenets that underpin it are flawed and showing why, far from doing good, cancer chemoprevention causes harm.
Publisher: Wiley
Date: 28-11-2010
DOI: 10.1002/IJC.25721
Publisher: Elsevier BV
Date: 08-2008
Publisher: American Medical Association (AMA)
Date: 16-12-2009
Publisher: American Association for Cancer Research (AACR)
Date: 12-2010
DOI: 10.1158/1055-9965.EPI-10-0878
Abstract: Background: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive. Methods: We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Women's Health Initiative (WHI) the Diet, Activity and Lifestyle Study (DALS) a Minnesota population-based case–control study (MinnCCS) and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene–environment interactions. Results: SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19 95% CI, 1.01–1.40 Ptrend = 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11 95% CI, 0.99–1.25 Ptrend = 0.07), and not associated in DALS and MinnCCS. Evaluating for gene–environment interactions yielded no consistent results across the studies. A meta-analysis of 17 studies (including these 4) gave an OR per A allele of 1.07 (95% CI, 1.03–1.12 Ptrend = 0.001). Conclusions: Our results suggest the Aallele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies. Impact: If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia. Cancer Epidemiol Biomarkers Prev 19(12) 3131–9. ©2010 AACR.
Publisher: American Medical Association (AMA)
Date: 18-02-2004
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22420551
Abstract: Table S1 shows similar results of interactions between BMI/smoking and NSAID use, using multiple imputation for missing values.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2015
Publisher: Springer Science and Business Media LLC
Date: 1994
DOI: 10.1007/BF01830725
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2014
DOI: 10.1038/CTG.2014.3
Publisher: Oxford University Press (OUP)
Date: 27-05-2004
DOI: 10.1093/IJE/DYH102
Publisher: Springer Science and Business Media LLC
Date: 05-2010
Publisher: Elsevier BV
Date: 2011
Publisher: Oxford University Press (OUP)
Date: 19-07-1995
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2004
DOI: 10.1097/01.GME.0000113932.56832.27
Abstract: To evaluate the effect of moderate-intensity exercise on the occurrence and severity of menopause symptoms. A yearlong, randomized, clinical trial, conducted in Seattle, WA, with 173 overweight, postmenopausal women not taking hormone therapy in the previous 6 months. The intervention was a moderate-intensity exercise intervention (n = 87) versus stretching control group (n = 86). Using logistic regression, odds ratios comparing exercise with controls were calculated at 3, 6, 9, and 12 months for menopause symptoms and their severity. There was a significant increase in hot flash severity and decreased risk of memory problems in exercisers versus controls over 12 months, although the numbers affected were small. No other significant changes in symptoms were observed. Exercise does not seem to decrease the risk of having menopause symptoms in overweight, postmenopausal women not taking hormone therapy and may increase the severity of some symptoms in a small number of women.
Publisher: Springer Science and Business Media LLC
Date: 10-06-2014
DOI: 10.1038/BJC.2014.309
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
Publisher: Oxford University Press (OUP)
Date: 08-07-2007
Abstract: Exposures such as cigarette smoke and meat contain a variety of procarcinogens, which are thought to play a role in elevation of risk for colorectal polyps and/or cancer. These procarcinogens (including heterocyclic amines and polycyclic aromatic hydrocarbons) are metabolized by a variety of polymorphic enzymes including N-acetyltransferases, sulfotransferases, cytochrome P450 enzymes and epoxide hydrolase. We hypothesized that genetic variation in the encoding genes NAT1, NAT2, SULT1A1, SULT1A2, CYP1A1 or EPHX1 is associated with risk of colorectal polyps and interacts with cigarette use or meat intake to modify risk of colorectal polyps. We examined the role of these genes in a clinic-based study of 651 Caucasian cases with hyperplastic polyps, adenomatous polyps or both types of polyps and 556 polyp-free controls. We found evidence for interaction between NAT acetylator status and SULT1A1 genotype in risk of hyperplastic polyps: in iduals with SULT1A1 638AA genotype and NAT1 and NAT2 intermediate/fast phenotypes had 3.5-fold increased risk (95% CI 1.2-10.3) compared with in iduals with SULT1A1 638GG genotype and NAT1 and NAT2 slow phenotypes. Data were also consistent with interactions between smoking and variation in SULT1A1, CYP1A1 and EPHX1 and between meat intake and variation in CYP1A1 and EPHX1. No interactions were statistically significant. Although results should be interpreted with caution considering s le size and the number of hypotheses examined, our study suggests future avenues of investigation in larger investigations of genetic and lifestyle factors in the pathway to colorectal cancer.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2010
Publisher: Wiley
Date: 27-01-1997
DOI: 10.1002/(SICI)1097-0215(19970127)70:3<259::AID-IJC2>3.0.CO;2-W
Abstract: Smoking cigarettes has been consistently associated with adenomatous polyps. However, only a few studies have reported associations between smoking cigarettes or using other forms of tobacco and colon cancer. A population-based case-control study of colon cancer was conducted in 3 areas in the United States: northern California, Utah and Minnesota. We observed approximately a 50% increase in colon cancer risk from smoking over a pack of cigarettes per day among both men and women. Those who stopped smoking remained at increased risk, even if they stopped over 10 years ago. Our data suggest that the amount smoked may be a more important factor than the total number of years smoked. Smoking neither cigars nor pipes was associated with an increased risk of colon cancer. Among female participants only, those who smoked over 20 cigarettes per day and had a large body mass index were at greater risk of colon cancer than participants who smoked the same amount but were smaller (p for interaction among women = 0.04).
Publisher: American Association for Cancer Research (AACR)
Date: 10-2008
DOI: 10.1158/1055-9965.EPI-08-0388
Abstract: Background: Experimental and epidemiologic studies have suggested that high calcium intake is associated with decreased colon cancer risk, yet very limited data are available for candidate genes in the calcium–vitamin D pathway and colon cancer risk. To address this, we evaluated whether calcium-sensing receptor (CASR) single-nucleotide polymorphisms are associated with colon cancer risk. We also examined interactions among CASR, calcium, and vitamin D intake and previously genotyped vitamin D–related genes. Methods: We conducted a large multicenter population-based case-control study of 1,600 cases and 1,949 controls. Seventeen tagging single-nucleotide polymorphisms for CASR were selected from common single-nucleotide polymorphisms (minor allele frequency, ≥5%) based on resequencing data. Haplotypes were estimated and evaluated using HaploStats. Results: We did not observe an association between any CASR genotypes or haplotypes and colon cancer risk overall. However, when stratified by anatomic site, statistically significant associations were seen with risk for proximal colon cancer [rs10934578 TT: odds ratio, 1.35 95% confidence interval (95% CI), 1.01-1.81 rs12485716 AG/AA: odds ratio, 0.84 95% CI, 0.71-1.00 rs4678174 CT/CC: odds ratio, 0.83 95% CI, 0.70-0.98 rs2270916 CC: odds ratio, 0.43 95% CI, 0.19-0.97]. Concordantly, we observed a suggested association for a CASR haplotype (rs4678174, rs2270916) with risk for proximal colon cancer (global P = 0.08). We did not observe any meaningful gene-environment (calcium and vitamin D) or gene-gene (CYP24A1, CYP27B1, and VDR) interactions with CASR genotypes and colon cancer risk. Conclusion: Our study does not provide evidence for an overall association between CASR single-nucleotide polymorphisms and colon cancer however, results suggest a possible role of CASR on proximal colon cancer, and subsite differences are consistent with known calcium biology. Nonetheless, these findings require confirmation. (Cancer Epidemiol Biomarkers Prev 2008 (10):2755–65)
Publisher: Environmental Health Perspectives
Date: 07-2005
DOI: 10.1289/EHP.7651
Abstract: New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a "toolbox" of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure-disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs.
Publisher: Oxford University Press (OUP)
Date: 1979
DOI: 10.1093/IJE/8.4.295
Abstract: Recent epidemiologically and experimental research has implicated dietary factors, including alcoholic drinks, in cancers of the colon and rectum. Analysis of time trends in cancer mortality since 1921, in the United States, England and Wales, Australia, and New Zealand, in relation to changes in per capita consumption of foodstuffs and alcohol reveals some support for the protective effect of fibre, but an inconsistent role for fat and meat in colon cancer. For rectal cancer, and to a lesser extent colon cancer, the most consistent correlate in comparisons across time, and between place, sex, and age-group, is beer consumption. Possible reasons for this correlation within this data set are discussed.
Publisher: Springer Science and Business Media LLC
Date: 10-1989
DOI: 10.1007/BF02106578
Publisher: Wiley
Date: 23-07-2002
DOI: 10.1002/CNCR.10695
Abstract: The association between method of detection and breast carcinoma histopathology has not been assessed adequately in a population-based setting. Among women who were included in a population-based, case-control study of breast cancer, patients who were newly diagnosed with invasive breast carcinoma were identified from Wisconsin's statewide tumor registry. Only women age > or = 50 years were analyzed, because screening by mammography was not recommended before age 50 years at the time of the study. The breast tumors among these women (n = 2341 tumors) included the following histopathologies: lobular carcinoma (n = 206 tumors) ductal carcinoma, not otherwise specified (n = 1920 tumors) papillary carcinoma (n = 15 tumors) medullary carcinoma (n = 36 tumors) mucinous adenocarcinoma (n = 56 tumors) tubular adenocarcinoma (n = 41 tumors) invasive comedocarcinoma (n = 24 tumors) scirrhous adenocarcinoma (n = 15 tumors) and mixed ductal/lobular carcinoma (n = 28 tumors). Overall, women reported that 41% of tumors were detected by mammography, 48% of tumors were self detected, and 11% of tumors were detected by clinical breast examination (CBE). Detection by mammography was significantly more likely for women who had tubular carcinoma (83% P or = 50 years, breast cancer detection by mammography, self detection, and CBE varied according to tumor histopathology.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-02-2015
Publisher: Oxford University Press (OUP)
Date: 24-05-2013
DOI: 10.1093/JNCI/DJT102
Publisher: Wiley
Date: 21-04-2008
DOI: 10.1002/CNCR.23405
Abstract: Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML). This analysis included 272 5-year AML survivors who participated in the Childhood Cancer Survivor Study (CCSS). All patients were diagnosed at age < or =21 years between the years 1970 and 1986, and none underwent stem cell transplantation. Rates of survival, relapse, and late outcomes were analyzed. The average follow-up was 20.5 years (range, 5-33 years). The overall survival rate was 97% at 10 years (95% confidence interval [95%CI], 94%-98%) and 94% at 20 years (95% CI, 90%-96%). Six survivors reported 8 recurrences. The cumulative incidence of recurrent AML was 6.6% at 10 years (95% CI, 3.7%-9.6%) and 8.6% at 20 years (95% CI, 5.1%-12.1%). Ten subsequent malignant neoplasms (SMN) were reported, including 4 with a history of radiation therapy, for a 20-year cumulative incidence of 1.7% (95% CI, 0.02%-3.4%). Six cardiac events were reported, for a 20-year cumulative incidence 4.7% (95% CI, 2.1%-7.3%). Half of the survivors reported a chronic medical condition and, compared with siblings, were at increased risk for severe or life-threatening chronic medical conditions (16% vs 5.8% P or =25 years, the age-adjusted marriage rates were similar among survivors and the general United States population (57% for both) and lower compared with siblings (67% P < .01). Survivors' college graduation rates were lower compared with siblings but higher than the general population (40% vs 52% vs 34%, respectively P or =5-years after diagnosis was favorable. Late-occurring medical events remained a concern with socioeconomic achievement lower than expected within the in idual family unit, although it was not different from the general United States population.
Publisher: Oxford University Press (OUP)
Date: 05-1997
Abstract: Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas. Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens. Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4) ethoxyresorufin O-deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6) p-nitrophenol hydroxylation and N-nitrosodimethyl-amine N-demethylation (P450 2E1) lauric acid omega-hydroxylation (P450 4A1) and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels P450 levels were <1% of liver. Microsomal benzidine rostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA-dependent DNA-binding of [3H]N-hydroxy-ABP) of pancreatic cytosols was high, about twothirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using 32P-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most s les. Moreover, in eight of 29 DNA s les, a major adduct was observed that was chromatographically identical to the predominant ABP-DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2010
Publisher: Oxford University Press (OUP)
Date: 02-09-2010
DOI: 10.1093/IJE/DYQ139
Publisher: Wiley
Date: 26-09-2022
DOI: 10.1111/HEX.13599
Abstract: Māori, Pasifika and Asian women are less likely to attend cervical screening and Māori and Pasifika women are more likely to be diagnosed with later‐stage cervical cancer than other women in Aotearoa New Zealand. This study—with under‐screened women taking part in a randomized‐controlled trial comparing self‐testing and standard screening—explored the acceptability of a human papillomavirus (HPV) self‐test kit and the preferred method for receiving it. Māori, Pasifika and Asian women ( N = 376) completed a cross‐sectional postal questionnaire. Twenty‐six women who had not accepted the trial invitation were interviewed to understand their reasons for nonparticipation. Most women found the self‐test kit easy and convenient to use and reported that they did not find it painful, uncomfortable or embarrassing. This was reflected in the preference for a self‐test over a future smear test on the same grounds. Most women preferred to receive the kit by mail and take the test themselves, rather than having it done by a doctor or nurse. There was a range of preferences relating to how to return the kit. Phone calls with nonresponders revealed that, although most had received the test kit, the reasons for not choosing to be involved included not wanting to, being too busy or forgetting. HPV self‐testing was acceptable for Māori, Pasifika and Asian women in Aotearoa New Zealand. HPV self‐testing has considerable potential to reduce the inequities in the current screening programme and should be made available with appropriate delivery options as soon as possible. This study explored the acceptability of HPV self‐testing and their preferences for engaging with it among Māori, Pasifika and Asian women. Thus, women from these underserved communities were the participants and focus of this study.
Publisher: Springer Science and Business Media LLC
Date: 11-1996
DOI: 10.1007/BF00051700
Abstract: Low temperature (LT) is an important factor limiting plant growth and distribution. Plants have evolved sophisticated adaptive mechanisms to cope with hypothermia. RNA silencing is the orchestrator of these cellular responses. RNA silencing, which modifies gene expression through noncoding RNAs (ncRNAs), is a strategy used by plants to combat environmental stress. ncRNAs, which have very little protein-coding capacity, work by binding reverse complementary endogenous transcripts. In plants, ncRNAs include small non-coding RNAs (sncRNAs), medium-sized non-coding RNAs (mncRNAs), and long non-coding RNAs (lncRNAs). Apart from describing the biogenesis of different ncRNAs (miRNAs, siRNAs, and lncRNAs), we thoroughly discuss the functions of these ncRNAs during cold acclimation. Two major classes of sncRNAs, microRNAs and siRNAs, play essential regulatory roles in cold response processes through the posttranscriptional gene silencing (PTGS) pathway or transcriptional gene silencing (TGS) pathway. Microarray or transcriptome sequencing analysis can reveal a large number of cold-responsive miRNAs in plants. In this review, the cold-response patterns of miRNAs verified by Northern blotting or quantitative PCR in
Publisher: Elsevier BV
Date: 08-2008
Publisher: American Association for Cancer Research (AACR)
Date: 10-2011
DOI: 10.1158/1055-9965.EPI-11-0391
Abstract: Although it is tacitly recognized that a good coordinating center (CC) is essential to the success of any multisite collaborative project, very little study has been done on what makes a CC successful, why some CCs fail, or how to build a CC that meets the needs of a given project. Moreover, very little published guidance is available, as few CCs outside the clinical trial realm write about their work. The Asia Cohort Consortium (ACC) is a collaborative cancer epidemiology research project that has made strong scientific and organizational progress over the past 3 years by focusing its CC on the following activities: collaboration development operations management statistical and data management and communications infrastructure and tool development. Our hope is that, by sharing our experience building the ACC CC, we can begin a conversation about what it means to run a CC for multi-institutional collaboration in cancer epidemiology, help other collaborative projects solve some of the issues associated with collaborative research, and learn from others. Cancer Epidemiol Biomarkers Prev 20(10) 2115–9. ©2011 AACR.
Publisher: Springer Science and Business Media LLC
Date: 15-08-2007
Abstract: To investigate cross-sectional and longitudinal relationships among exercise, sleep, ghrelin and leptin. We randomly assigned 173 post-menopausal sedentary overweight (body mass index >or=24.0 kg/m(2) and >33% body fat) women aged 50-75 years living in western Washington State to either a facility- and home-based moderate-intensity physical activity intervention or a stretching control group. Fasting plasma ghrelin, leptin, measured height, weight and self-reported sleep were assessed at baseline and 12 months. There were no consistent cross-sectional patterns between self-reported sleep measures and ghrelin or leptin at baseline. The weight loss differences between exercisers and stretchers were greater for those who slept less at follow-up than at baseline compared to those whose sleep duration did not change (-3.2 kg, 95% confidence interval (CI) -5.8, -0.5). Improvements in sleep quality were associated with significantly greater differences between exercisers and stretchers for ghrelin increases (improved vs same sleep quality: +115 pg/ml, 95% CI +25, +206) and leptin decreases (improved vs worsened sleep quality: -5.7 ng/ml, 95% CI -9.5, -1.5). There was only limited evidence that changes in sleep duration or quality modified exercise-induced changes in weight, ghrelin or leptin. Moreover, the observed differences were not in the directions hypothesized. Future longitudinal studies including population-based s les using objective measures of sleep and long follow-up may help to clarify these relationships.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22420548
Abstract: Table S2 shows no significant differences were observed between regular use of NSAIDs and CRC risk across cancer subsites or stages.
Publisher: American Association for Cancer Research (AACR)
Date: 12-2005
DOI: 10.1158/1055-9965.EPI-05-0514
Abstract: Estrogen and androgens are thought to be involved in the etiology of colorectal cancer. We evaluate genetic variants of the estrogen receptor genes (ERα and ERβ) and the androgen receptor gene (AR). We use data from two large case-control studies of colon (n = 1,580 cases and 1,968 controls) and rectal (n = 797 cases and 1,016 controls) cancer. We evaluated the 351A& G XbaI polymorphism of ERα, the 1,082 G& A and CA repeat polymorphisms of ERβ, and the CAG repeat of AR. Having two 25 or more CA repeats in ERβ was associated with an increased relative risk of colon cancer in women [odds ratio (OR), 2.13 95% confidence interval (95% CI), 1.24-3.64] but not in men (Pinteraction relative excess risk from interaction & 0.01 multiplicative = 0.03). Increasing number of AR CAG repeats was directly associated with colon cancer among men (OR, 1.28 95% CI, 1.06-1.54), but not women (OR, 0.83 95% CI, 0.68-1.02) the interaction P value for AR gene × sex was & .01. Taking hormone replacement therapy (HRT) was associated with a reduced risk of colon cancer in the presence of the R allele of the ERβ gene, whereas an R allele was associated with increased risk among postmenopausal women who did not take HRT. Postmenopausal women not using HRT who had ≥25 CA repeats of the ERβ gene had over a 6-fold increased risk of colon cancer (OR, 6.71 95% CI, 2.89-15.6). Our results suggest that the ERβ gene is more important than ERα in the etiology of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2005 (12):2936–42)
Publisher: Informa UK Limited
Date: 05-04-2010
Publisher: American Association for Cancer Research (AACR)
Date: 08-2007
DOI: 10.1158/0008-5472.CAN-06-4275
Abstract: Current users of postmenopausal hormones (PMH) have ∼30% to 40% lower risk of colorectal cancer (CRC), although associations with specific types of hormones have been inconsistent. Further, it is not clear whether some tumor types have a different risk. We conducted a case-control study to examine the relationship between PMH and CRC. Cases (n = 1,004), ages 50 to 74 years, were identified from the Surveillance Epidemiology and End Results registry in Washington from 1998 to 2002 controls (n = 1,062) were randomly selected from population lists. Case tissue s les were obtained for microsatellite instability (MSI) analyses. Interviews collected risk-factor data for CRC, including detailed information on PMH. Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (95% CI). Current use of any PMH was associated with a 20% reduction in CRC risk (95% CI 0.6–0.9). This reduction in risk was limited to women who had taken estrogen plus progestin (EP) preparations only (OR = 0.6, 95% CI 0.5–0.9) there was no association with estrogen-only (E alone) use (OR = 0.9, 95% CI 0.7–1.1). For women with MSI-low or MSI-stable tumors, there was a statistically significant 40% reduction in CRC risk associated with EP use (95% CI 0.4–0.9) there was no clear association with MSI-high tumors. EP use was associated with a decreased risk of CRC however, there seemed to be no association with E alone data that are consistent with the recent Women's Health Initiative findings. Progestin may enhance the estrogenic effect of conjugated estrogen so the combination may be more biologically active in the colon than E alone. [Cancer Res 2007 (15):7534–9]
Publisher: Wiley
Date: 09-07-2008
DOI: 10.1002/GCC.20584
Publisher: Springer Science and Business Media LLC
Date: 04-2006
DOI: 10.1007/S10552-005-0411-6
Abstract: We hypothesize that the peroxisome proliferator-activated receptor-gamma (PPARgamma) is associated with colorectal cancer given its association with insulin, diabetes, obesity, and inflammation. In this study, we evaluated the association between colorectal cancer and specific tumor mutations and the Pro12Ala (P12A) PPARgamma polymorphism. We also evaluated interactions between the PPARgamma gene and other insulin-related genes and use of aspirin and non-steroidal anti-inflammatory drug use. Data were available from 1,577 cases of colon cancer that were matched to 1,971 population-based controls and 794 cases of rectal cancer that were matched to 1,001 population-based controls. Colon tumors from the case subjects were evaluated for p53 and Ki-ras mutations and microsatellite instability (MSI). Insulin-related genes evaluated were the Bsm1, polyA, and Fok1 polymorphisms of the VDR gene the G972R IRS1 polymorphism the G1057D IRS2 polymorphism the 19CA repeat polymorphism of the IGF1 gene and the -200A>C IGFBP3 polymorphism. The odds ratio (OR) between the PA/AA genotypes and proximal tumors was 0.83 (95% CI: 0.69-1.01) for distal tumors was 1.00 (95% CI: 0.83-1.21) and for rectal tumors was 1.04 (95% CI: 0.86-1.25). Evaluation of specific types of tumor mutations showed that colon cancer cases with the PA or AA genotypes were less likely to have p53 tumor mutations (OR 0.78 95% CI: 0.62-0.99), specifically transition mutations (OR 0.74 95% CI: 0.56-0.97). Colon cancer cases also were less likely to have a tumor with MSI if they had the PA or AA PPARgamma genotype (OR 0.68 95% CI: 0.47-0.98) differences in Ki-ras mutations were not seen in colon tumors by PPARgamma genotype. Those who did not take ibuprofen-type drugs and had the PA or AA genotypes were at a significantly greater risk of rectal cancer (OR 2.11 95% CI: 1.52-2.92 p interaction 0.03) than people with the PP genotype regardless of ibuprofen-type drug use. There was a significant interaction between the -200A>C IGFBP3 polymorphism and the Pro12Ala PPARgamma polymorphism and risk of colon cancer (p for interaction = 0.02) with in iduals being at significantly lower risk if they had both the CC IGFBP3 genotype and the PA/AA PPARgamma genotype. For rectal cancer there was a significant interaction between the Bsm1 olyA polymorphisms (p = 0.001) of the VDR gene and the PA/AA Pro12Ala PPARgamma polymorphism with the highest risk group being those with both the PA/AA Pro12Ala PPARgamma and the BB/SS VDR genotypes. These data suggest that PPARgamma may be associated with many aspects of colorectal cancer including insulin- and inflammation-related mechanisms.
Publisher: Wiley
Date: 1995
Abstract: Inheritance of a major susceptibility gene for breast cancer has been primarily investigated in families with early-onset disease. However, familial clustering of late-onset breast cancer is well documented, and genetic factors may also be relevant. In the Iowa Women's Health Study, we evaluated evidence for a major gene after allowing for measured environmental risk factors. Two hundred sixty-five incident breast cancer probands were identified from a prospective cohort study of 41,837 women aged 55 to 69 years at baseline in 1986. A pedigree development form was mailed to the probands to ascertain all first-degree female relatives. A questionnaire and body measurement protocol were mailed to identified living relatives or surrogates. Segregation analyses were conducted on a total of 1,145 women in 251 families using regressive models as implemented in S.A.G.E. Mendelian codominant inheritance of an allele that produced an earlier-age-at-onset provided the best fit to the data. Incorporation of measured environmental risk factors as covariates yielded no significant improvements in the likelihoods. Approximately 50% of this population could be expected to carry a late-onset breast cancer susceptibility gene, and 23% of the population is susceptible because of the environment in which they live. Homozygous gene carriers are predicted to have a mean age-at-onset of 48 years, over 20 years earlier than heterozygotes few cases would be expected among non-gene carriers. In conclusion, the transmission pattern of late-onset breast cancer may be determined by a common susceptibility gene.
Publisher: Wiley
Date: 1995
Abstract: In 1944, a case-control family study was initiated at the Dight Institute for Human Genetics at the University of Minnesota to study the influences of childbearing breastfeeding, and hereditary susceptibility on the occurrence and age-of-onset of breast cancer. Index cases (probands) were women ascertained at the Tumor Clinic of the University of Minnesota Hospital. Medical history and life style information were obtained on probands and relatives, and all cancers were histologically verified. A total of 544 families were studied, with probands diagnosed between 1931 and 1952. All of the records and pathology slides have been maintained from the original study for most probands this includes the original tissue blocks. We are conducting a historical cohort study of selected of selected first- and second-degree female relatives (sisters, daughters, nieces, granddaughters) of the probands and a group of control women identified as the spouses of all male first- and second-degree relatives (brothers, sons, grandsons, and nephews). The subsequent development of breast cancer is being determined to quantify the absolute risk associated with a positive family history. Current disease status is ascertained with mammography, and stromal density is measured using digital imaging. Segregation analysis will be applied to examine how non-genetic factors such as diet, exogenous hormone use, and body fat distribution influence risk in women at high risk because of family history. A subset of families are being selected for molecular analysis of the BRCA1 gene or for linkage analyses to identify putative susceptibility loci other than BRCA1. Documented cancer histories were known for at least three generations, and the current study extends the pedigrees up to four or five generations for every family, allowing a detailed description of familial risk. This cohort study of breast cancer families is likely to be important in both quantity and quality of data and will serve as a major genetic epidemiologic resource, being free of selection bias and having relevant non-genetic exposure determined in at least four generations.
Publisher: Springer Science and Business Media LLC
Date: 31-07-2001
Publisher: Environmental Health Perspectives
Date: 03-2009
DOI: 10.1289/EHP.11580
Publisher: Oxford University Press (OUP)
Date: 07-04-2005
Abstract: Apolipoprotein E (apoE) plays a major role in the metabolism of bile acids, cholesterol and triglycerides, and has recently been proposed as being involved in the carcinogenic process. Given the potential role of bile acids in colorectal cancer etiology, it is reasonable that colorectal cancer risk might be modified by apoE genotype. We used data collected from a case-control study of colon cancer (n=1556 cases and 1948 controls) and rectal cancer (n=777 cases and 988 controls). The absence of an e3 apoE allele significantly increased the risk of colon cancer (OR=1.37 95% CI 1.00-1.87), particularly among those diagnosed when older than 64 years (OR=1.88 95% CI 1.17-3.04 P interaction between age and apoE genotype equal to 0.05). A significant three-way interaction was detected for family history of colorectal cancer, age at diagnosis and apoE genotype (P = 0.05), in those diagnosed when older, not having an e3 allele and having a significantly increased risk of colon cancer with family history of colorectal cancer (OR=3.93 95% CI 1.23-12.6). This was compared with the risk associated with family history of colorectal cancer among those diagnosed when older, with an e3 allele of 1.61 (95% CI 1.17-2.23) or those diagnosed when younger without an e3 allele (OR=2.40 95% CI 0.56-10.3). Among those diagnosed when older than 64 years, associations of BMI and prudent diet with colon cancer were stronger among in iduals without an e3 allele, although the P for interaction was not significant. We did not detect any significant associations between apoE genotype and rectal cancer, survival after diagnosis with colorectal cancer, stage of disease at diagnosis or type of tumor mutation. These findings suggest those apoE genotypes that do not include the e3 allele, the same genotypes that are associated with increased risk of coronary heart disease, may influence development of colon cancer among those who are older at diagnosis.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426021.V1
Abstract: Supplementary Table S5
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 28-10-2006
Abstract: Acetylsalicylic acid (aspirin) is a common nonsteroidal anti-inflammatory drug used for treatment of pain and arthritis. In the body, acetylsalicylic acid is rapidly deacetylated to form salicylic acid. Both compounds have been proposed as anti-inflammatory agents. Major metabolites of salicylic acid are its acyl and phenolic glucuronide conjugates. Formation of these conjugates, catalyzed by UDP-glucuronosyltransferases (UGTs), decreases the amount of pharmacologically active salicylic acid present. We aimed to identify the UGTs catalyzing the glucuronidation of salicylic acid using both heterologously expressed enzymes and pooled human liver microsomes (HLMs) and to develop a liquid chromatography-tandem mass spectrometry method to quantify glucuronidation activity of UGTs 1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15, and 2B17 Supersomes. All UGTs tested, except 1A4, 2B15, and 2B17, catalyzed salicylic acid phenolic and acyl glucuronidation. Ratios of salicylic acid phenolic to acyl glucuronide formation varied more than 12-fold from 0.5 for UGT1A6 to 6.1 for UGT1A1. These results suggest that all UGTs except 1A4, 2B15, and 2B17 might be involved in the glucuronidation of salicylic acid in vivo. From comparisons of apparent Km values determined in pooled HLMs and in expressed UGTs, UGT2B7 was suggested as a likely catalyst of salicylic acid acyl glucuronidation, whereas multiple UGTs were suggested as catalysts of phenolic glucuronidation. The results of this UGT screening may help target future evaluation of the effects of UGT polymorphisms on response to aspirin in clinical and population-based studies.
Publisher: BMJ
Date: 09-08-2013
Publisher: Public Library of Science (PLoS)
Date: 06-10-2014
Publisher: American Association for Cancer Research (AACR)
Date: 11-2013
DOI: 10.1158/1055-9965.EPI-13-0209
Abstract: Background: Experimental evidence has demonstrated an antineoplastic role for vitamin D in the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D. Methods: We investigated whether five polymorphisms in GC, CYP2R1, CYP24A1, and DHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with colorectal cancer risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We conducted a meta-analysis of crude and multivariate-adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs in idually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS). Results: We did not observe a statistically significant association between the 25(OH)D-associated SNPs and colorectal cancer marginally, conditionally, or as a GRS, or for colon or rectal cancer separately. Conclusions: Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of colorectal cancer. Additional work is warranted to investigate the complex relationship between 25(OH)D and colorectal cancer risk. Impact: There was no association observed between genetic markers of circulating 25(OH)D and colorectal cancer. These genetic markers account for a small proportion of the variance in 25(OH)D. Cancer Epidemiol Biomarkers Prev 22(11) 2037–46. ©2013 AACR.
Publisher: Springer Science and Business Media LLC
Date: 13-02-2023
Publisher: Springer Science and Business Media LLC
Date: 27-02-2006
Abstract: Methotrexate (MTX) is used as an immunosuppressive agent for acute graft-versus-host disease (GVHD) prophylaxis following hematopoietic cell transplantation (HCT). Concerns that folate intake may impair MTX effectiveness or selectively rescue leukemic cells have led to variations in clinical practice regarding supplemental folic acid during MTX administration. A retrospective, observational study was undertaken to determine the association between folic acid intake (days 0-18 post transplant) and MTX toxicity and efficacy following HCT. The study population consisted of 311 adult patients who received a myeloablative HCT for chronic myelogenous leukemia, all four scheduled doses of MTX, and did not require leucovorin rescue. Multiple linear regression models were used to assess the relationships between folic acid intake (days 0-18 post-HCT) and oral mucositis index (OMI) scores, time to engraftment and risk of detectable acute GVHD. No statistically significant differences in mean OMI scores, time to engraftment, risk of acute GVHD, days to acute GVHD, risk of relapse or survival were observed when comparing patients taking, on average, 400 microg (28%) folic acid per day. Our results suggest that concurrent folic acid supplementation does not change MTX effectiveness or toxicity in this patient population.
Publisher: Cold Spring Harbor Laboratory
Date: 04-2022
DOI: 10.1101/2022.03.29.22273037
Abstract: Māori, Pasifika, and Asian women are less likely to attend cervical screening and Māori and Pasifika women are more likely to be diagnosed with later-stage cervical cancer than other women in Aotearoa New Zealand. This study – with under-screened women taking part in a randomised controlled trial comparing self-testing and standard screening – explored the acceptability of an HPV self-test kit and the preferred method for receiving it. Māori, Pasifika, and Asian women (N=376) completed a postal questionnaire. Twenty-six women who had not accepted the trial invitation were interviewed to understand their reasons for non-participation. Most women found the self-test kit easy and convenient to use and reported that they did not find it painful, uncomfortable, or embarrassing. This was reflected in the preference for a self-test over a future smear test on the same grounds. Most women preferred to receive the kit by mail and take the test themselves, rather than having it done by a doctor or nurse. There was a range of preferences relating to how to return the kit. Phone calls with non-responders revealed that, although most had received the test kit, the reasons for not choosing to be involved included not wanting to, being too busy, or forgetting. HPV self-testing was acceptable for Māori, Pasifika, and Asian women in Aotearoa New Zealand. HPV self-testing has considerable potential to reduce the inequities in the current screening programme and should be made available with appropriate delivery options as soon as possible.
Publisher: Oxford University Press (OUP)
Date: 05-2002
Publisher: Oxford University Press (OUP)
Date: 31-08-2004
DOI: 10.1093/JNCI/DJH240
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2005
DOI: 10.1097/01.EDE.0000165363.27323.AC
Abstract: Recent studies suggest that diet records are more valid measures of nutrient intake than are food-frequency questionnaires. However, food records are considered unsuitable for large studies due to the need to train participants and to review and correct completed records. We evaluated a self-administered 3-day food record protocol in Washington State. One hundred men and women age 50-76 years were mailed a food record and serving-size booklet. Sixty-five people returned a completed food record and were subsequently interviewed to obtain missing information. The food records were analyzed with and without added information from the interview. The most common error was incomplete description, which affected 8% of recorded foods. Differences in mean nutrient intake between the uncorrected and corrected records were within 5%, and nutrient estimates from the 2 methods were highly correlated. This streamlined protocol yielded data comparable to those collected by more burdensome protocols, suggesting that the use of food records may be feasible in large cohort studies.
Publisher: Elsevier BV
Date: 10-2013
Publisher: Springer Science and Business Media LLC
Date: 26-06-2023
DOI: 10.1038/S41416-023-02312-Z
Abstract: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. We used data from 3 genetic consortia (CCFR, CORECT, GECCO 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 – OR AA : 1.62, 95% CI: 1.34–1.96 OR AG : 1.41, 95% CI: 1.30–1.54 OR GG : 1.22, 95% CI: 1.13–1.31 p -value 3-d.f. : 5.46 × 10 −11 ) and 13q14.13 (rs9526201, LRCH1 – OR GG : 2.11, 95% CI: 1.56–2.83 OR GA : 1.52, 95% CI: 1.38–1.68 OR AA : 1.13, 95% CI: 1.06–1.21 p -value 2-d.f. : 7.84 × 10 −09 ). These results suggest that variation in genes related to insulin signaling ( SLC30A8 ) and immune function ( LRCH1 ) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2019
DOI: 10.1158/1055-9965.EPI-19-0389
Abstract: To date, few epidemiologic studies have been conducted to elucidate lifestyle-related risk factors for multiple myeloma in Asia. We investigated the association of body mass index (BMI), smoking, and alcohol intake with the risk of multiple myeloma mortality through a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium. The analysis included 805,309 participants contributing 10,221,623 person-years of accumulated follow-up across Asia Cohort Consortium cohorts. HRs and 95% confidence intervals (95% CI) for the association between BMI, smoking, and alcohol at baseline and the risk of multiple myeloma mortality were assessed using a Cox proportional hazards model with shared frailty. We observed a statistically significant dose-dependent association between BMI categories and the risk of multiple myeloma mortality (& .5 kg/m2: HR = 0.80, 95% CI: 0.52–1.24 18.5–24.9 kg/m2: reference 25.0–29.9 kg/m2: HR = 1.17, 95% CI: 0.94–1.47 ≥30 kg/m2: HR = 1.61, 95% CI: 0.99–2.64, Ptrend = 0.014). By sex, this association was more apparent in women than in men (P for heterogeneity between sexes = 0.150). We observed no significant associations between smoking or alcohol consumption and risk of multiple myeloma mortality. This study showed that excess body mass is associated with an increased risk of multiple myeloma mortality among Asian populations. In contrast, our results do not support an association between smoking or alcohol consumption and the risk of multiple myeloma mortality in Asian populations. This study provides important evidence on the association of BMI, smoking, and alcohol with the risk of multiple myeloma mortality in Asian populations.
Publisher: American Association for Cancer Research (AACR)
Date: 10-2011
DOI: 10.1158/1055-9965.EPI-11-0450
Abstract: Background: While some studies have reported detection of oncogenic human papillomavirus (HPV) in colorectal tumors, others have not. Methods: We examined the association between oncogenic HPV infection and colorectal polyps in a case–control study of in iduals with colorectal adenomas (n = 167), hyperplastic polyps (n = 87), and polyp-free controls (n = 250). We carried out real-time PCR for HPV-16 and -18 DNA, and SPF PCR covering 43 HPV types, on lesional and normal colorectal tissue s les. Plasma antibodies for oncogenic HPV types were assessed via a bead-based multiplex Luminex assay. Results: HPV DNA was not found in any of the 609 successfully assayed colorectal tissue s les from adenomas, hyperplastic polyps, normal biopsies adjacent to polyps, or normal biopsies of the rectum of disease-free controls. Also, there was no association between HPV seropositivity for all oncogenic HPV types combined, for either polyp type, and for men or women. When analyses were restricted to participants without a history of polyps, among men [adenomas (n = 31), hyperplastic polyps (n = 28), and controls (n = 68)], there was an association between seropositivity and hyperplastic polyps when all oncogenic HPV types were combined (OR = 3.0 95% CI: 1.1–7.9). Conclusions: Overall, our findings do not support an etiologic relationship between HPV and colorectal adenomas or hyperplastic polyps however, our finding suggesting an association between HPV seropositivity and hyperplastic polyps in men may warrant further investigations. Impact: After stringent controls for contamination and three methods to assess HPV infection, we report no evidence for HPV in the etiology of colorectal neoplasia for either men or women. Cancer Epidemiol Biomarkers Prev 20(10) 2288–97. ©2011 AACR.
Publisher: MDPI AG
Date: 30-10-2020
DOI: 10.3390/MICROORGANISMS8111698
Abstract: Previously, we found that risk of colorectal cancer (CRC) is increased in in iduals with serum antibody response to both Helicobacter pylori (HP) Vacuolating Cytotoxin (VacA) toxin or Streptococcus gallolyticus (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts. To examine whether combined SGG Gallo2178 and HP VacA sero-status was associated with CRC risk, we used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to dual sero-negative in iduals, there was no increased risk for in iduals sero-positive to SGG Gallo2178 only (OR: 0.93 95% CI: 0.66–1.31) or to HP VacA only (OR: 1.08 95% CI: 0.98–1.19). However, dual sero-positive in iduals had a % increased odds of developing CRC (OR: 1.54 95% CI: 1.16–2.04), suggesting an interaction between antibody responses to these two pathogens and CRC risk (pinteraction = 0.06). In conclusion, this study suggests that dual sero-positivity to HP VacA and SGG Gallo2178 is an indicator of increased risk of CRC.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2007
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426012.V1
Abstract: Supplementary Text
Publisher: Massachusetts Medical Society
Date: 21-01-1999
Publisher: Elsevier BV
Date: 04-2009
Publisher: Oxford University Press (OUP)
Date: 03-09-2020
DOI: 10.1093/JNCI/DJAA058
Abstract: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18 P = 9.75 × 10–17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32 P = 2.13 × 10–24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827 Pobserved = .0009 Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10–10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32 P = 2.60 × 10–10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19 P = 1.04 × 10–8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14 P = .02) genotypes. These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2006
DOI: 10.1158/1055-9965.EPI-05-0814
Abstract: Inherited variants of the vitamin D receptor (VDR) gene may influence cancer risk by altering the effect of vitamin D on cell growth and homeostasis. Studies have examined genotypes for common VDR polymorphisms, including a single nucleotide polymorphism (SNP) detected by Bsm1, a polyadenosine [poly(A)] repeat polymorphism, and a SNP detected by Fok1, as candidates for susceptibility to cancer, but most have not evaluated haplotypes for these markers. We investigated haplotypes for these polymorphisms in case-control studies of colon cancer (1,811 cases and 1,451 controls) and rectal cancer (905 cases and 679 controls). We used the expectation-maximization algorithm to estimate haplotypes for White, Hispanic, African-American, and Asian subjects, tested for differences in VDR haplotype distribution, and calculated odds ratios (OR) for association between haplotype and cancer. The distribution of haplotypes differed by race or ethnic group, but four common haplotypes accounted for the majority of alleles in all groups. VDR haplotype distributions differed between colon cancer cases and controls (P = 0.0004). The common haplotype bLF, containing Bsm1 b (Bsm1 restriction site present), poly(A) long (18-22 repeats), and Fok1 F (restriction site absent) was associated with increased risk of colon cancer, OR 1.15 (95% confidence interval, 1.03-1.28), as was the rare haplotype BLF, containing Bsm1 B (restriction site absent), poly(A) long, and Fok1 F (OR, 2.40 95% confidence interval, 1.43-4.02). No case-control differences were detected for rectal cancer. In this analysis, haplotypes of the VDR influenced risk of colon cancer, but haplotype variables had only slightly better ability to explain case-control differences than genotype variables. (Cancer Epidemiol Biomarkers prev 2006 (4):744–9)
Publisher: American Association for Cancer Research (AACR)
Date: 05-2007
Publisher: American Association for Cancer Research (AACR)
Date: 18-03-2021
DOI: 10.1158/1055-9965.EPI-20-1471
Abstract: The association between prediagnostic antibody responses to Fusobacterium nucleatum (F. nucleatum) and subsequent risk of colorectal cancer is not established. We conducted a nested case–control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States. Higher seroprevalence of any F. nucleatum antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight F. nucleatum proteins and colorectal cancer risk. Prediagnostic antibody responses to F. nucleatum proteins were not associated with the risk of colorectal cancer. Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining F. nucleatum in stool or tissue s les.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426024.V1
Abstract: Supplementary Table S4
Publisher: Elsevier BV
Date: 11-2021
Publisher: BMJ
Date: 04-11-2010
Publisher: American Association for Cancer Research (AACR)
Date: 12-2009
DOI: 10.1158/1055-9965.EPI-09-0955
Abstract: DNA repair enzymes function in major pathways to reverse DNA damage, including base excision repair (BER). Missense polymorphisms in BER repair genes may contribute to differences in DNA repair capacity, specific mutations, and susceptibility to cancer in the presence of exposure to carcinogens such as cigarette smoking. In a study of 1,604 incident colon cancer cases and 1,969 matched population-based controls genotyped for BER variants OGG1 (S326C) and XRCC1 (R194W, R280H, and R399Q), we found no associations with colon cancer overall. However, a 2-fold increased risk of BRAF V600E tumor mutation was observed in current and former cigarette smokers homozygous for the OGG1 polymorphism (odds ratio, 2.2 95% confidence interval, 1.02-4.9, recessive model) similar associations were not observed for microsatellite instability, CpG island methylator phenotype, KRAS2 mutations, or TP53 mutations. The XRCC1 R194W polymorphism was associated with a modest increased risk of TP53 tumor mutations in those who regularly smoked cigarettes (odds ratio, 1.4 95% confidence interval, 1.02-1.9). These findings point to the importance of studying tumor mutations when examining DNA repair polymorphisms and cigarette smoke exposure to identify potentially relevant associations with colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2009 (12):3384–8)
Publisher: Oxford University Press (OUP)
Date: 15-09-2002
DOI: 10.1093/AJE/KWF082
Abstract: Anthropometric characteristics, physical activity, and risk of non-Hodgkin's lymphoma, its subtypes, and B-cell chronic lymphocytic leukemia (B-CLL) were evaluated in a prospective cohort study of 37,931 Iowa women who were aged 55-69 years at baseline in 1986. Through 1998, 261 cases of non-Hodgkin's lymphoma (137 diffuse, 58 follicular, and 32 small lymphocytic lymphomas) and 63 cases of B-CLL were identified by linkage to the Iowa Cancer Registry. Height, weight, body mass index, waist/hip ratio, and physical activity were not associated with risk of non-Hodgkin's lymphoma overall or with diffuse or follicular lymphoma in particular. After adjustment for other non-Hodgkin's lymphoma risk factors, there was an inverse association of baseline body mass index (relative risks (RRs) across quartiles: 1, 0.4, 0.4, 0.3 p trend = 0.03) with risk of small lymphocytic lymphoma. In contrast, for B-CLL there were suggestive positive associations with body mass index at age 50 years (RRs across quartiles: 1, 1.9, 1.5, 2.7 p trend = 0.03) and (more weakly) baseline body mass index (RRs across quartiles: 1, 1.1, 1.6, 1.3 p trend = 0.3). In summary, we found no evidence that height, weight, body mass, or physical activity plays an important role in non-Hodgkin's lymphoma overall or in diffuse or follicular lymphoma in particular. The opposite associations of body mass index with small lymphocytic lymphoma versus B-CLL may be a chance finding but, if confirmed, would suggest different etiologies for these malignancies.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2015
DOI: 10.1158/1055-9965.EPI-14-0756
Abstract: Background: Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor β (ESR2) has been associated with colorectal cancer stage and survival. Methods: In this prospective cohort study, we examined smoking, MHT, and folate-associated colorectal cancer risks by ESR2 protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded colorectal cancer tissue specimens were collected and evaluated for ESR2 protein expression by IHC. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between smoking, MHT, or folate and ESR2-defined colorectal cancer subtypes. Results: Informative environmental exposure and protein expression data were available for 491 incident colorectal cancer cases. Positive associations between ESR2-low and -high tumors and several smoking-related variables were noted, most prominently with average number of cigarettes per day (RR, 4.24 95% CI, 1.81–9.91 for ESR2-low and RR, 2.15 95% CI, 1.05–4.41 for ESR2-high for ≥40 cigarettes compared with nonsmokers). For MHT, a statistically significant association with ESR2-low tumors was observed with longer duration of exposure (RR, 0.54 95% CI, 0.26–1.13 for & years compared with never use). No associations were found for folate. Conclusions: In this study, smoking and MHT were associated with ESR2 expression patterns. Impact: These data support possible heterogeneous effects from smoking and MHT on ERβ-related pathways of colorectal carcinogenesis in older women. Cancer Epidemiol Biomarkers Prev 24(4) 713–9. ©2015 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 05-2009
DOI: 10.1158/1055-9965.EPI-08-1088
Abstract: Background: Epidemiologic studies suggest a reduced risk of breast cancer among women who regularly use aspirin a plausible mechanism is through aspirin effect on mammographic breast density, a breast cancer risk factor, possibly mediated through aspirin interference with estrogen synthesis. Methods: In a 2-arm randomized placebo-controlled clinical trial, we evaluated the effects of 6-month administration of 325 mg/day aspirin on total mammographic breast dense area and percent of the mammographic breast image occupied by dense areas (% density) in 143 postmenopausal women. Eligible women, recruited from 2005 to 2007, were healthy, not taking hormone therapy, with elevated mammographic breast density (American College of Radiology Breast Imaging Reporting and Data System density category 2, 3, or 4) within 6 months before enrollment. Results: Women were a mean (SD) 59.5 (5.5) years. Geometric mean baseline percent density was 17.6% (95% confidence interval, 14.8-20.9) in women randomized to aspirin and 19.2% (95% confidence interval, 16.3-22.7) in women randomized to placebo. Percent density decreased in women randomized to aspirin by an absolute 0.8% versus an absolute decrease of 1.2% in controls (P = 0.84). Total breast area and dense area decreased to a similar degree in women assigned to aspirin and in those assigned to placebo, with no statistically significant differences between trial arms. Conclusions: A single daily administration of adult-dose aspirin for 6 months had no effect on mammographic density in postmenopausal women. If aspirin affects breast cancer risk in postmenopausal women, it may do so through alternative pathways than mammographic breast density. (Cancer Epidemiol Biomarkers Prev 2009 (5):1524–30)
Publisher: American Association for Cancer Research (AACR)
Date: 09-2007
DOI: 10.1158/1055-9965.EPI-07-0291
Abstract: Background: Cellular proliferation and apoptosis (cell death) are highly regulated in the colon as insufficient apoptosis may lead to polyps and cancer. Physical activity decreases risk of colon cancer in observational studies, but the biological basis is not well defined. The objective of this study is to examine the effects of a 12-month aerobic exercise program on expression of proteins that promote (Bax) or inhibit (Bcl-2) apoptosis in colon crypts. Methods: Two hundred two sedentary participants, 40 to 75 years, were randomly assigned to moderate-to-vigorous intensity exercise for 60 min per day, 6 days per week for 12 months, or usual lifestyle. Colon crypt s les were obtained at baseline and 12 months. Bcl-2 and Bax expression was measured by immunohistochemistry. Results: Bax density at the bottom of crypts increased in male exercisers versus controls (+0.87 versus −0.18 P = 0.05), whereas the ratio of Bcl-2 to Bax at the bottom and middle of crypts decreased as aerobic fitness (VO2max) increased (P trend = 0.02 and 0.05, respectively). In female exercisers, Bax density in the middle of crypts decreased (−0.36 versus +0.69 P = 0.03) and Bcl-2 to Bax ratio at the top of crypts increased versus controls (+0.46 versus −0.85 P = 0.03). Bax density in the middle of crypts also decreased as minutes per week of exercise increased (P trend = 0.03). Conclusions: A 12-month exercise intervention resulted in greater expression of proteins that promote apoptosis at the bottom of colon crypts in men and decreased expression of proteins that promote apoptosis at the middle and top of colon crypts in women. The difference in effect by gender and location of observed changes warrants further study. (Cancer Epidemiol Biomarkers Prev 2007 (9):1767–74)
Publisher: Elsevier BV
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 1993
DOI: 10.1007/BF00051710
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6512209
Abstract: Abstract Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in i BRAF /i and i KRAS /i genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of i BRAF /i -mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65–1.04)] but not i BRAF /i -wildtype tumors [1.09 (0.97–1.22) i P /i difference as shown in case-only analysis = 0.02]. This difference was observed in case–control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, i BRAF /i -wildtype, and i KRAS /i -wildtype tumors ( i P /i sub trend /sub range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, i BRAF /i -mutated, or i KRAS /i -mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. Significance: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported. /
Publisher: Springer Science and Business Media LLC
Date: 12-2010
Publisher: American Association for Cancer Research (AACR)
Date: 12-2010
DOI: 10.1158/1055-9965.EPI-10-0942
Abstract: Introduction: Chronic inflammation may be important in prostate carcinogenesis. Several epidemiologic studies have reported inverse associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and prostate cancer risk, although many studies are limited by assessment of short-term use only. Methods: Participants were male members of the VITamins And Lifestyle cohort, comprised 34,132 men, aged 50–76 years, living in western Washington State. Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) of 10-year average use of in idual NSAIDs with total prostate cancer (n = 1,550) and prostate cancer by grade. Results: Low-dose aspirin, regular-strength aspirin, ibuprofen, and any nonaspirin NSAID (ibuprofen, naproxen, and COX-2 inhibitors) were not associated with prostate cancer risk. There was a suggestion that regular-strength aspirin was inversely associated with risk of high-grade cancer (HR 0.73, 95% CI: 0.53–1.02). Conclusion: NSAID use was not associated with prostate cancer risk in the VITAL cohort. Impact: Our findings do not support the use of NSAIDs for chemoprevention of prostate cancer. Cancer Epidemiol Biomarkers Prev 19(12) 3185–8. ©2010 AACR.
Publisher: Oxford University Press (OUP)
Date: 2004
DOI: 10.1093/AJE/KWH010
Abstract: Vitamin and mineral supplements are among the most commonly used drugs in the United States, despite limited evidence on their benefits or risks. This paper describes the design, implementation, and participant characteristics of the VITamins And Lifestyle (VITAL) Study, a cohort study of the associations of supplement use with cancer risk. A total of 77,738 men and women in western Washington State, aged 50-76 years, entered the study in 2000-2002 by completing a detailed questionnaire on supplement use, diet, and other cancer risk factors, and 70% provided DNA through self-collected buccal cell specimens. Supplement users were targeted in recruitment: 66% used multivitamins, 46% used in idual vitamin C, 47% used in idual vitamin E, and 46% used calcium, typically for 5-8 of the past 10 years. Analyses to identify confounding factors, the main study limitation, showed that regular nonsteroidal anti-inflammatory drug use, intake of fruits and vegetables, and recreational physical activity were strongly associated with supplement use (p < 0.001). The authors describe a follow-up system in which cancers, deaths, and changes of residence are tracked efficiently, primarily through linkage to public databases. These methods may be useful to other researchers implementing a large cohort study or designing a passive follow-up system.
Publisher: Mary Ann Liebert Inc
Date: 07-2009
Publisher: American Association for Cancer Research (AACR)
Date: 03-2005
Publisher: Oxford University Press (OUP)
Date: 02-2002
Abstract: The authors previously reported an interaction of waist/hip ratio and family history on the risk of breast cancer in the Iowa Women's Health Study. Here they reexamine this association based on 9 additional years of follow-up, stratifying on tumor receptors for estrogen and progesterone. Data on risk factors and family history of breast cancer were ascertained in 1986. The occurrences of breast cancer and estrogen receptor rogesterone receptor were determined through the Iowa Surveillance, Epidemiology, and End Results' registry. Rate ratios were elevated with increasing weight and body mass index and decreasing body mass index at age 18 years, but they did not vary by family history. There was no association with height, waist circumference, or waist/hip ratio. A linear trend of increasing risk with increasing waist/hip ratio was observed among family history-positive women (p = 0.06) but not among family history-negative women (p = 0.87). This apparent interaction (p = 0.09) was examined by estrogen receptor or progesterone receptor status. When stratified on family history and estrogen receptor, no clear patterns were evident. In contrast, family history-positive women in the upper quintile of the waist/hip ratio were at 2.2-fold greater risk of progesterone receptor-negative tumors compared with those in the lowest quintile (95% confidence interval: 0.9, 5.8). Thus, the previously reported interaction between family history and waist/hip ratio is still (weakly) evident and appears to reflect risk for progesterone receptor-negative tumors.
Publisher: Springer Science and Business Media LLC
Date: 2002
Abstract: Endogenous sex hormones, particularly estrogens, modulate the immune system, and non-Hodgkin lymphoma (NHL) is a tumor that is related to immunologic status. Self-reported menstrual and reproductive history and risk of NHL were evaluated in a cohort of 37,934 Iowa women who were aged 55-69 years when first enrolled in 1986. Through 1998, 261 cases of NHL were identified by linkage to the Iowa SEER Cancer Registry. After multivariate adjustment there was no association between NHL incidence and age at menarche, age at menopause, type of menopause, history of infertility, number of miscarriages, or history of induced abortion, while there were suggestive inverse associations with nulliparity (RR=0.65 95% CI 0.36-1.16) and years of ovulation (RR = 0.76 for >37 compared to 2 children versus none 95% CI 0.33-0.82). Overall, menstrual and reproductive factors were not strongly related to NHL incidence. The inverse association with breast-feeding is novel but requires confirmation in other studies.
Publisher: American Association for Cancer Research (AACR)
Date: 2004
DOI: 10.1158/1055-9965.EPI-03-0026
Abstract: Women with high circulating estrogen concentrations have an increased risk of breast cancer thus, it is important to understand factors, including genetic variability, that influence estrogen concentrations. Several genetic polymorphisms that may influence sex hormone concentrations have been identified, including CYP17 (5′-untranslated region T→C), CYP19 [intron 4 (TTTA)n = 7–13 and a 3-bp deletion (−3)], CYP1B1 (Val432Leu), and COMT (Val108/158Met). We examined associations between these polymorphisms and serum concentrations of estrogens, androgens, and sex hormone-binding globulin and urinary concentrations of 2- and 16α-hydroxyestrone in 171 postmenopausal women, using data from the prerandomization visit of an exercise clinical trial. Participants were sedentary, not taking hormone therapy, and had a body mass index & .0. Compared with noncarriers, women carrying two CYP19 7r(−3) alleles had 26% lower estrone (P & 0.001), 19% lower estradiol (P = 0.01), 23% lower free estradiol (P = 0.01), and 22% higher sex hormone-binding globulin concentrations (P = 0.06). Compared with noncarriers, women carrying at least one CYP19 8r allele had 20% higher estrone (P = 0.003), 18% higher estradiol (P = 0.02), and 21% higher free estradiol concentrations (P = 0.01). Women with the COMT Met/Met genotype had 28% higher 2-hydroxyestrone (P = 0.08) and 31% higher 16α-hydroxyestrone concentrations (P = 0.02), compared with Val/Val women. Few associations were found for CYP17 and CYP1B1 or with serum androgen concentrations. This study provides further evidence that genetic variation may appreciably alter sex hormone concentrations in postmenopausal women not taking hormone therapy.
Publisher: Elsevier BV
Date: 11-1999
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6512209.V1
Abstract: Abstract Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in i BRAF /i and i KRAS /i genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of i BRAF /i -mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65–1.04)] but not i BRAF /i -wildtype tumors [1.09 (0.97–1.22) i P /i difference as shown in case-only analysis = 0.02]. This difference was observed in case–control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, i BRAF /i -wildtype, and i KRAS /i -wildtype tumors ( i P /i sub trend /sub range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, i BRAF /i -mutated, or i KRAS /i -mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. Significance: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported. /
Publisher: Elsevier BV
Date: 08-2005
Publisher: Elsevier BV
Date: 04-2012
Publisher: American Association for Cancer Research (AACR)
Date: 20-04-2021
DOI: 10.1158/1055-9965.EPI-20-1690
Abstract: Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses. The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-s le MR. In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk the MR analyses showed a greater risk for women (OR per 1-SD = 1.09 95% CI, 1.01–1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16 95% CI, 1.05–1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational and MR analyses. Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development. Our results from large-scale analyses provide little evidence for sex hormone pathways playing a causal role in colorectal cancer development. See related commentary by Hang and Shen, p. 1302
Publisher: Elsevier BV
Date: 12-2003
Publisher: American Association for Cancer Research (AACR)
Date: 09-01-2023
DOI: 10.1158/1055-9965.EPI-22-0817
Abstract: Polygenic risk scores (PRS) which summarize in iduals’ genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance. The model was developed using 20,338 in iduals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in in iduals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group). In European-ancestral in iduals, the predicted 5-year risk calibrated well [E/O = 1.01 95% confidence interval (CI), 0.91–1.13] and had high discriminatory accuracy (AUC = 0.73 95% CI, 0.71–0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P & 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P & 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity. The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort. The proposed model has potential utility in risk-stratified colorectal cancer prevention.
Publisher: Japan Epidemiological Association
Date: 2012
Publisher: Springer Science and Business Media LLC
Date: 13-08-2007
Publisher: Wiley
Date: 05-10-1998
DOI: 10.1002/(SICI)1097-0215(19981005)78:2<157::AID-IJC6>3.0.CO;2-Y
Abstract: The Diet, Activity, and Reproduction in Colon Cancer (DARCC) study is a large, multi-center case-control study of colon cancer. We examined family histories of cancer among first-degree relatives obtained by computer-assisted in-person interviews from the DARCC to study the impact of family histories of several cancers and colorectal polyps on colon cancer risk. We examined familial cancer risks both by treating a family history of polyps or cancer as a covariate in a logistic regression model, and by comparing cancer or polyp incidence among relatives of cases to incidence among relatives of controls in a proportional hazards model. There were few differences between the odds ratios (OR) or confidence intervals (CI) generated from logistic regression models and the hazard rate ratios (HRR) generated from the proportional hazards models. Overall, the OR of colon cancer among subjects with a family history of colorectal cancer was 1.77. There were only minor differences in risk by sex, age and subsite. A family history of colorectal polyps also increased risk by about the same amount as a family history of colorectal cancer. The increased risk associated with a family history of polyps did not appear to decrease with age.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426036.V1
Abstract: Supplementary Table S1
Publisher: Elsevier BV
Date: 03-1997
DOI: 10.1016/S0304-3835(97)04697-1
Abstract: KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting
Publisher: American Association for Cancer Research (AACR)
Date: 11-2009
DOI: 10.1158/1055-9965.EPI-09-0701
Abstract: Glutathione S-transferases (GST) detoxify a wide range of carcinogens. Isothiocyanates (ITC), from cruciferous vegetables, are substrates for and inducers of GST. GST variants may alter ITC clearance such that response to crucifers varies by genotype. In a randomized cross-over trial, we tested the hypothesis that changes in serum GSTA1/2 concentration in response to cruciferous vegetable feeding depends on GSTM1/GSTT1 genotype. Thirty-three men and 34 women (age 20-40 years) ate four 14-day controlled diets—basal (vegetable-free), basal supplemented with two different doses of crucifers (“single dose” and “double dose”), and single-dose cruciferous-plus-apiaceous vegetables—fed per kilogram of body weight. Fasting bloods from days 0, 7, 11, and 14 of each diet period were analyzed for serum GSTA1/2 by ELISA. GSTA1/2 increased with single- and double-dose cruciferous compared with basal diet (10% and 13%, respectively P = 0.02 and 0.004), but cruciferous-plus-apiaceous did not differ from basal (P = 0.59). Overall, GSTA1/2 was higher in GSTM1-null/GSTT1-null than GSTM1+/GSTT1+ in iduals (4,198 ± 338 and 3,372 ± 183 pg/mL P = 0.03). The formal interaction of genotype-by-diet was not statistically significant, but the GSTA1/2 increase during the single-dose cruciferous diet was among GSTM1-null/GSTT1-null in iduals (by 28% P = 0.008), largely explained by GSTM1-null/GSTT1-null men (by 41% P = 0.01). GSTA1/2 increased during the double-dose cruciferous diet in both GSTM1-null/GSTT1-null men (by 35% P = 0.04) and GSTM1+/GSTT1+ men (by 26% P = 0.01) but not in women. In summary, cruciferous vegetable supplementation increased GSTA1/2, but the effect was most marked in GSTM1-null/GSTT1-null men. (Cancer Epidemiol Biomarkers Prev 2009 (11):2974–8)
Publisher: American Medical Association (AMA)
Date: 09-04-2003
Publisher: Oxford University Press (OUP)
Date: 15-05-2003
DOI: 10.1093/AJE/KWG039
Abstract: In the United States, dietary supplements contribute a large proportion of micronutrient intakes. Therefore, it is important to collect accurate information on supplement use for studies of micronutrients and disease risk. This report describes the test-retest reliability and validity of a detailed, self-administered mailed questionnaire on vitamin and mineral supplement use. Participants (n = 220) completed the questionnaire at baseline and 3 months later. During an in-person interview, participants provided spot urine and blood s les, and interviewers transcribed nutrient information from their supplement bottle labels. The questionnaire had very good test-retest reliability for mean supplement intake over the past 10 years, with intraclass correlations ranging from 0.69 for beta-carotene to 0.87 for vitamin E. Pearson's correlation coefficients comparing current supplemental intakes from the questionnaire and interviews/label transcriptions were high, ranging from 0.58 for beta-carotene to 0.82 for chromium however, for some nutrients, median intakes from the questionnaire were slightly lower than from the interviews. Beta-carotene, vitamin C, and vitamin E (alpha-tocopherol) showed clear linear trends of increasing blood concentrations with higher self-reported supplemental intakes (Pearson's correlation coefficients adjusted for potential confounding factors and diet = 0.31, 0.29, and 0.69, respectively all p < 0.0001). Creatinine-adjusted spot urinary calcium values were not associated with supplemental calcium intakes (Pearson's r = -0.07). This self-administered questionnaire demonstrated high reproducibility and validity for collecting detailed information on supplement use.
Publisher: Springer Science and Business Media LLC
Date: 03-01-2012
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/0008-5472.C.6769316.V1
Abstract: Abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 ( i FMN1/GREM1 /i ) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the i FMN1/GREM1 /i gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies. /
Publisher: American Association for Cancer Research (AACR)
Date: 07-2008
DOI: 10.1158/1055-9965.EPI-08-0088
Abstract: Low-grade systemic inflammation is suggested to play a role in the development of several chronic diseases including cancer. Higher levels of physical activity and lower adiposity have been associated with reduced levels of markers of systemic inflammation, such as C-reactive protein (CRP) however, reductions in CRP have not been consistently observed in randomized controlled trials of exercise. Purpose: To examine the effect of a 12-month aerobic exercise intervention on CRP levels in men and women. Methods: One hundred two men and 100 women, sedentary and of ages 40 to 75 years, with mean body mass index (BMI) of 29.9 and 28.7 kg/m2, respectively, were randomly assigned to a 12-month moderate-to-vigorous aerobic exercise intervention (6 d/wk, 60 min/d, 60-85% maximum heart rate) or control group. Fasting blood s les were collected at baseline and at 12 months. CRP levels were measured by high-sensitivity latex-enhanced nephelometry. Results: At baseline, CRP was 1.16 and 2.11 mg/L for men and women, respectively, and CRP was correlated with percent body fat (r = 0.48, P ≤0.001), BMI (r = 0.37, P ≤ 0.001), and aerobic fitness (r = −0.49, P ≤ 0.001). No intervention effects were observed for CRP in men or women, or when stratified by baseline BMI (& versus ≥30 kg/m2), baseline CRP (& versus ≥3 mg/L), or change in body weight, body composition, or aerobic fitness. Conclusion: A 12-month moderate-to-vigorous aerobic exercise intervention did not affect CRP levels in previously sedentary men or women with average-risk CRP values at baseline. (Cancer Epidemiol Biomarkers Prev 2008 (7):1714–8)
Publisher: Oxford University Press (OUP)
Date: 1990
DOI: 10.1093/HER/5.4.479
Publisher: Oxford University Press (OUP)
Date: 17-03-2010
DOI: 10.1093/JNCI/DJQ011
Publisher: Elsevier BV
Date: 03-2021
Publisher: Springer Science and Business Media LLC
Date: 2002
Abstract: Phase II metabolizing enzymes such as glutathione S-transferases and N-acetyltransferase are involved in the detoxification of carcinogens. Genetic variants of genes coding for these enzymes have been evaluated as to their association with colon cancer, both as independent risk factors and as effect modifiers for associations with diet and cigarette smoking. In this study, we evaluate associations between the GSTM-1 genotype and the NAT2-imputed phenotype and acquired mutations in tumors. Data is taken from a set of 1836 cases and 1958 controls with colon cancer who were part of a large case-control study of colon cancer and whose tumors were previously analyzed for Ki-ras, p53, and microsatellite instability (MSI). We also evaluate the modifying effects of these genetic variants with diet and cigarette smoking, factors previously identified as being associated with specific tumor alterations. Neither GSTM-1 nor the NAT2-imputed phenotype was independently associated with Ki-ras, p53, or MSI. Cigarette smoking significantly increased the risk of tumors involving the MSI pathway. Additionally, cigarette smoking doubled the risk of p53 transversion mutations among those who were GSTM-1 present. Cases were slightly more likely to have a p53 mutation if they frequently consumed red meat and had the imputed NAT2 intermediate/rapid phenotype relative to slow phenotype/infrequent consumers of red meat (OR 2.0, 95% CI 1.3-3.0 for intermediate/rapid). These data provide support that diet and cigarette smoking may be associated with specific disease pathways, although GSTM-1 and NAT2 do not independently appear to alter susceptibility to these diet and lifestyle factors.
Publisher: Informa UK Limited
Date: 25-01-2010
Publisher: Springer Science and Business Media LLC
Date: 07-1995
DOI: 10.1007/BF00051404
Publisher: Elsevier BV
Date: 10-2014
Publisher: American Association for Cancer Research (AACR)
Date: 14-02-2010
DOI: 10.1158/0008-5472.CAN-08-1792
Abstract: Genome-wide association studies (GWAS) have identified SMAD7 on 8q21 as being associated with colorectal cancer. We evaluated single nucleotide polymorphisms (SNP) in the SMAD7 gene, including rs4939827, rs12953717, and rs4464148, previously identified from GWAS in a large population-based case-control study of colon cancer. We observed that rs12953717 was associated with a statistically significant increased risk of colon cancer [odds ratio, 1.38 95% confidence intervals (CI), 1.13–1.68 P linear trend & 0.01] for the TT genotype compared with the CC genotype, whereas the CC genotype of the rs4939827 SNP was inversely associated with colon cancer (0.77 95% CI, 0.64–0.93) relative to the TT genotype. There were no significant differences in association for either of these polymorphisms when stratified by age, tumor site, sex, or family history. The odds ratios between SMAD7 and colon cancer among in iduals reporting recent aspirin/nonsteroidal anti-inflammatory drug use was 0.60 (95% CI, 0.43–0.85) for the CC genotype of the rs4939827 polymorphism and 1.69 (95% CI, 1.20–2.38) for the TT genotype of the rs1295371 polymorphism. This result compares to odds ratios of 0.86 (95% CI, 0.68–1.09) for rs4939827 and 1.22 (95% CI, 0.96–1.56) among in iduals who did not use aspirin/nonsteroidal anti-inflammatory drugs. An assessment of SMAD7 genotypes with tumor markers did not reveal any significant differences by KRAS2, TP53, CpG island methylator phenotype, or microsatellite instability status. No significant associations were observed for the rs4464148 SNP or other SNPs evaluated in the SMAD7. These results corroborate the findings of GWAS in colon cancer pointing to SMAD7 and reinforce interest in SNPs in this gene. Cancer Res 70(4) 1479–85
Publisher: Elsevier BV
Date: 05-1995
DOI: 10.1016/1047-2797(94)00113-8
Abstract: Response rates are an important component of epidemiologic research. The purposes of this study are (a) to evaluate how response rates are defined and calculated for control subjects in epidemiologic case-control studies, and (b) to explore factors that may impact response in epidemiologic studies. Our results show that the method of control subject selection has an impact on study response. Gender of respondent does not appear to impact response rates. However, response rates are generally worse for in iduals less than 45 years old. Methods used to calculate response have a great impact on "response rate" therefore, it is important for researchers to define exactly what the reported response rates represent and how they are derived so that data can be interpreted appropriately.
Publisher: Baishideng Publishing Group Inc.
Date: 2013
Publisher: Oxford University Press (OUP)
Date: 07-06-2014
Publisher: Springer Science and Business Media LLC
Date: 19-03-2013
DOI: 10.1038/BJC.2013.118
Publisher: American Association for Cancer Research (AACR)
Date: 30-06-2010
DOI: 10.1158/0008-5472.CAN-10-0188
Abstract: Genetic risk factors are important contributors to the development of colorectal cancer. Following the definition of a linkage signal at 9q22-31, we fine mapped this region in an independent collection of colon cancer families. We used a custom array of single-nucleotide polymorphisms (SNP) densely spaced across the candidate region, performing both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. Through this approach, we isolated the association effect to a five-SNP haplotype centered at 98.15 Mb on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to GALNT12, also recently shown to be altered in colon tumors. We used a predictive modeling algorithm to show the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (odds ratio, 3.68), and the accuracy of our prediction model (∼60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q. Cancer Res 70(13) 5409–18. ©2010 AACR.
Publisher: Elsevier BV
Date: 03-1997
DOI: 10.1016/S0304-3835(97)04694-6
Abstract: Vegetables and fruits are associated with a reduced risk of cancers, including especially lung cancer. The possible protective compounds include a wide variety of phytochemicals. However, for historical, technical, and biological reasons, a great deal of attention has focused on a single agent: beta-carotene. Recently, in clinical trials, beta-carotene has been shown not to be an effective agent and, perhaps, to be harmful. Possible explanations for this are presented, as is the danger of reductionist approaches to the explanation of the complex nutrition-related biology of cancer.
Publisher: Oxford University Press (OUP)
Date: 22-09-2012
Publisher: Oxford University Press (OUP)
Date: 29-05-2014
DOI: 10.1093/AJE/KWU114
Publisher: Springer Science and Business Media LLC
Date: 1999
Abstract: Substantial decline of ovarian hormones at menopause plays an important role in breast cancer etiology. Hormones must bind to specific receptors to elicit biological responses, however. We therefore hypothesized and examined whether the age-specific risk of breast cancer, especially its change at menopause, differs by estrogen and progesterone receptor (ER/PR) status. Age-specific incidence rates, stratified by ER/PR status, were estimated by multiplying the age-specific ER/PR distribution among 3359 cases in the Danish Breast Cancer Cooperative Group by Danish national age-specific incidence rates. International variations in the age-incidence curve were also reviewed in relation to the hypothesis. The incidence of ER +/PR + subtype (62.9% of all cases) increased with age continually, with a sudden decrease in the rate of increase around age 44. The incidence of ER-/PR- subtype (17.6%) increased with age prior to about age 50 but remained unchanged subsequently. The incidence of ER+ /PR- subtype (13.9%) increased rapidly during the menopausal period but only slightly afterwards. The incidence of ER-/PR+ subtype (5.6%) increased until about age 43 and decreased subsequently. The international comparison revealed Western women, particularly the elderly, might be at substantially higher risk for ER+ /PR+ subtype compared to Japanese women. Age-specific risk of breast cancer differs by ER/PR status. The large international variation of breast cancer incidence rates may be explained largely by the risk difference for ER+ /PR+ subtype.
Publisher: American Association for Cancer Research (AACR)
Date: 10-2009
DOI: 10.1158/1055-9965.EPI-09-0517
Abstract: Introduction: Both smoking and alcohol consumption have been associated with modestly increased risks of colorectal cancer (CRC). Reports have suggested that these associations may differ by tumor molecular subtype, with stronger associations for microsatellite unstable (MSI-H) tumors. Methods: We used a population-based case-unaffected sibling design including 2,248 sibships (2,253 cases 4,486 siblings) recruited to the Colon Cancer Family Registry to evaluate the association between smoking, alcohol consumption, and CRC. Associations were assessed using conditional logistic regression, treating sibship as the matching factor. Results: Although there were no statistically significant associations between any smoking variable and CRC overall, smoking did confer an increased risk of certain types of CRC. We observed an association between pack-years of smoking and rectal cancer [odds ratio (OR), 1.85 95% confidence interval (CI), 1.23-2.79 for & pack-years versus nonsmokers Ptrend = 0.03], and there was an increased risk of MSI-H CRC with increasing duration of smoking (OR, 1.94 95% CI, 1.09-3.46 for & years of smoking versus nonsmokers). Alcohol intake was associated with a modest increase in risk for CRC overall (OR, 1.21 95% CI, 1.03-1.44 for 12+ drinks per week versus nondrinkers), with more marked increases in risk for MSI-L CRC (OR, 1.85 95% CI, 1.06-3.24) and rectal cancer (OR, 1.48 95% CI, 1.08-2.02). Conclusions: We found associations between cigarette smoking and increased risks of rectal cancer and MSI-H CRC. Alcohol intake was associated with increased risks of rectal cancer and MSI-L CRC. These results highlight the importance of considering tumor phenotype in studies of risk factors for CRC. (Cancer Epidemiol Biomarkers Prev 2009 (10):2745–50)
Publisher: Wiley
Date: 20-03-2014
DOI: 10.1002/IJC.28823
Publisher: American Society of Hematology
Date: 10-2001
Publisher: American Association for Cancer Research (AACR)
Date: 15-02-2010
DOI: 10.1158/1078-0432.CCR-09-1877
Abstract: Purpose: Lynch syndrome family members with inherited germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), and cases typically have tumors that exhibit a high level of microsatellite instability (MSI). There is some evidence that smoking is a risk factor for CRCs with high MSI however, the association of smoking with CRC among those with Lynch syndrome is unknown. Experimental Design: A multicentered retrospective cohort of 752 carriers of pathogenic MMR gene mutations was analyzed, using a weighted Cox regression analysis, adjusting for sex, ascertainment source, the specific mutated gene, year of birth, and familial clustering. Results: Compared with never smokers, current smokers had a significantly increased CRC risk [adjusted hazard ratio (HR), 1.62 95% confidence interval (95% CI), 1.01-2.57] and former smokers who had quit smoking for 2 or more years were at decreased risk (HR, 0.53 95% CI, 0.35-0.82). CRC risk did not vary according to age at starting. However, light smoking (& cigarettes per day) and shorter duration of smoking (& years) were associated with decreased CRC risk (HR, 0.51 95% CI, 0.29-0.91 and HR, 0.52 95% CI, 0.30-0.89, respectively). For former smokers, CRC risk decreased with years since quitting (P trend & .01). Conclusions: People with Lynch syndrome may be at increased risk of CRC if they smoke regularly. Although our data suggest that former smokers, short-term smokers, and light smokers are at decreased CRC risk, these findings need further confirmation, preferably using prospective designs. Clin Cancer Res 16(4) 1331–9
Publisher: American Association for Cancer Research (AACR)
Date: 03-2005
DOI: 10.1158/1055-9965.EPI-04-0058
Abstract: Several characteristics of aberrant crypt foci (ACF) suggest that they are precursors of colorectal cancer, but the factors that promote or inhibit their growth are largely unknown. We conducted a pilot study to explore whether factors associated with risk of colorectal cancer are also associated with number or size of rectal ACF. Thirty-two U.S. veterans, ages 50 to 80 years, were recruited to undergo magnifying chromoendoscopy for imaging of rectal ACF and colonoscopy for identification of polyps or cancer. Participants completed a questionnaire on cigarette smoking, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and family history of colorectal cancer. Fisher's exact test was used to assess the statistical significance of associations between colorectal cancer risk factors and characteristics of ACF. Cochran-Mantel-Haenszel statistics and polytomous regression were used to test the significance of associations adjusted for age. Participants with a history of adenoma had more ACF than those without (age-adjusted P = 0.02), but the numbers in the two groups overlapped markedly. Older participants had more (P = 0.06) and larger (P = 0.009) ACF than younger participants. No associations were identified between either ACF number or size and cigarette smoking, use of NSAIDs, or family history of colorectal cancer. These findings suggest that persons with adenomas have somewhat more rectal ACF than persons without, and that older age is a risk factor for ACF growth. Future research should be directed toward developing techniques to identify ACF that are likely to progress to cancer and the modifiable factors that promote or inhibit such progression.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2015
Publisher: Wiley
Date: 25-01-2008
DOI: 10.1002/IJC.23135
Publisher: Elsevier BV
Date: 08-2012
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6510681.V1
Abstract: Abstract Nonsteroidal anti-inflammatory drugs’ (NSAID) use has consistently been associated with lower risk of colorectal cancer however, studies showed inconsistent results on which cohort of in iduals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on colorectal cancer risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions. Regular use of any NSAID, aspirin, or nonaspirin NSAIDs was significantly associated with a lower risk of colorectal cancer within almost all subgroups. However, smoking status and BMI were found to modify the NSAID–colorectal cancer association. Aspirin use was associated with a 29% lower colorectal cancer risk among never-smokers [odds ratios (OR) = 0.71 95% confidence intervals (CI): 0.64–0.79], compared with 19% and 17% lower colorectal cancer risk among smokers of pack-years below median (OR, 0.81 95% CI, 0.71–0.92) and above median (OR, 0.83 95% CI, 0.74–0.94), respectively ( i P /i interaction = 0.048). The association between any NSAID use and colorectal cancer risk was also attenuated with increasing BMI ( i P /i interaction = 0.075). Collectively, these results suggest that obese in iduals and heavy smokers are unlikely to benefit as much as other groups from the prophylactic effect of aspirin against colorectal cancer. b Significance: /b Obesity and heavy smoking attenuate the benefit of aspirin use for colorectal cancer prevention. i Cancer Res 78(16) 4790–9. ©2018 AACR /i . /
Publisher: Springer Science and Business Media LLC
Date: 02-2006
DOI: 10.1038/NRC1801
Abstract: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) show indisputable promise as chemopreventive agents. Possible targets include cancers of the colon, stomach, breast and lung. However, recent studies raise concern about potential cardiovascular toxicity associated with the use of NSAIDs that specifically target the enzyme cyclooxygenase 2. These findings, and others that show that inherited genetic characteristics might determine preventive success, argue for new strategies that are tailored to in idual medical history and genetic make-up.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Oxford University Press (OUP)
Date: 29-04-2010
Publisher: Springer Science and Business Media LLC
Date: 04-01-2013
Publisher: American Association for Cancer Research (AACR)
Date: 09-2020
DOI: 10.1158/1055-9965.EPI-19-1018
Abstract: Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk. Genetically predicted gene expressions were tested for interaction with NSAID use on colorectal cancer risk among 19,258 colorectal cancer cases and 18,597 controls from 21 observational studies. A Mixed Score Test for Interactions (MiSTi) approach was used to jointly assess G × E effects which are modeled via fixed interaction effects of the weighted burden within each gene set (burden) and residual G × E effects (variance). A false discovery rate (FDR) at 0.2 was applied to correct for multiple testing. Among the 4,840 genes tested, genetically predicted expression levels of four genes modified the effect of any NSAID use on colorectal cancer risk, including DPP10 (PG×E = 1.96 × 10−4), KRT16 (PG×E = 2.3 × 10−4), CD14 (PG×E = 9.38 × 10−4), and CYP27A1 (PG×E = 1.44 × 10−3). There was a significant interaction between expression level of RP11-89N17 and regular use of aspirin only on colorectal cancer risk (PG×E = 3.23 × 10−5). No interactions were observed between predicted gene expression and nonaspirin NSAID use at FDR & 0.2. By incorporating functional information, we discovered several novel genes that interacted with NSAID use. These findings provide preliminary support that could help understand the chemopreventive mechanisms of NSAIDs on colorectal cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 02-2010
DOI: 10.1158/1055-9965.EPI-09-0869
Abstract: Background: Prostaglandins are important inflammatory mediators prostaglandin E2 (PGE2) is the predominant prostaglandin in colorectal neoplasia and affects colorectal carcinogenesis. Prostaglandins are metabolites of ω-6 and ω-3 polyunsaturated fatty acids their biosynthesis is the primary target of nonsteroidal anti-inflammatory drugs (NSAID), which reduce colorectal neoplasia risk. Methods: We investigated candidate and tagSNPs in PGE2 synthase (PGES), PGE2 receptors (EP2 and EP4), and prostaglandin dehydrogenase (PGDH) in a case-control study of adenomas (n = 483) versus polyp-free controls (n = 582) and examined interactions with NSAID use or fish intake, a source of ω-3 fatty acids. Results: A 30% adenoma risk reduction was observed for EP2 4950G& A (intron 1 ORGA/AA vs. GG, 0.71 95% confidence interval, 0.52-0.99). For the candidate polymorphism EP4 Val294Ile, increasing fish intake was associated with increased adenoma risk among those with variant genotypes, but not among those with the Val/Val genotype (Pinteraction = 0.02). An interaction with fish intake was also observed for PGES −664A& T (5′ untranslated region Pinteraction = 0.01). Decreased risk with increasing fish intake was only seen among those with the AT or TT genotypes (OR& t/wk vs. & t/wk, 0.56 95% confidence interval, 0.28-1.13). We also detected interactions between NSAIDs and EP2 9814C& A (intron 1) and PGDH 343C& A (intron 1). However, none of the observed associations was statistically significant after adjustment for multiple testing. We investigated potential gene-gene interactions using the Chatterjee 1 degree of freedom Tukey test and logic regression neither method detected significant interactions. Conclusions: These data provide little support for associations between adenoma risk and genetic variability related to PGE2, yet suggest gene-environment interactions with anti-inflammatory exposures. Cancer Epidemiol Biomarkers Prev 19(2) 547–57
Publisher: Wiley
Date: 27-02-2012
DOI: 10.1002/GCC.21946
Publisher: American Association for Cancer Research (AACR)
Date: 02-2006
Publisher: Wiley
Date: 06-07-2009
DOI: 10.1002/MC.20566
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2009
Publisher: American Association for Cancer Research (AACR)
Date: 12-2020
DOI: 10.1158/1055-9965.EPI-20-0780
Abstract: Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53. In this study, we sought to examine this association in a U.S. colorectal cancer cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for colorectal cancer. Auto-antibodies to p53 were measured in prediagnostic blood s les of 3,702 incident colorectal cancer cases and 3,702 controls, matched by age, race, and sex, from 9 U.S. prospective cohorts. The association of seropositivity to p53 with colorectal cancer risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression. Overall, 5% of controls and 7% of cases were seropositive to p53, resulting in a statistically significant 33% increased colorectal cancer risk [odds ratio (OR), 1.33 95% confidence interval (CI), 1.09–1.61]. By follow-up time, the association was only significant with colorectal cancer diagnoses within 4 years after blood draw (OR, 2.27 95% CI, 1.62–3.19), but not thereafter (OR, 0.97 95% CI, 0.76–1.24). In this large consortium of prospective cohorts, we found that prediagnostic seropositivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing colorectal cancer within 4 years after blood draw. Our finding suggests that p53 seropositivity may not be a useful predictor of long-term colorectal cancer risk however, it might be considered as a marker to aid in the early diagnosis of colorectal cancer.
Publisher: American Society of Hematology
Date: 07-2001
Abstract: This study investigated whether a polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T) modifies responses to methotrexate (MTX) in patients undergoing bone marrow transplantation. About 10% to 12% of the population carry the MTHFR TT genotype (enzyme activity, 30% of wild type [CC]). Patients (n = 220) with chronic myelogenous leukemia underwent marrow allografts and were given a short course of MTX. MTX toxicity measures included the oral mucositis index (OMI), speed of engraftment (platelet and granulocyte counts), and bilirubin. Patients with lower MTHFR activity (TT genotype) had 36% higher mean OMI during days 1 to 18 (+5.7, P = .046) and 20% higher OMI between days 6 and 12 (+3.8, P = .27). Platelet counts recovered more slowly among patients with the TT genotype compared to wild type (24% slower recovery to 10 000 platelets/μL, P = .23 34% slower to 20 000/μL, P = .08). Patients with decreased MTHFR activity appear at risk of higher MTX toxicity. Because of the high prevalence of the TT genotype, these results may have implications for MTX dosage.
Publisher: Oxford University Press (OUP)
Date: 1990
DOI: 10.1093/HER/5.4.489
Publisher: Elsevier BV
Date: 05-1982
DOI: 10.1016/S0140-6736(82)92260-7
Abstract: Activating mutations in the adapter protein CARD11 associated with diffuse large B cell lymphomas (DLBCLs) are predicted to arise during germinal center (GC) responses, leading to inappropriate activation of NF-κB signaling. Here, we modeled the B cell-intrinsic impact of the L251P activating mutation in CARD11 (aCARD11) on the GC response. Global B cell aCARD11 expression led to a modest increase in splenic B cells and a severe reduction in B1 B cell numbers, respectively. Following T cell-dependent immunization, aCARD11 cells exhibited increased rates of GC formation, resolution, and differentiation. Restriction of aCARD11 to GC B cells similarly altered the GC response and B cell differentiation. In this model, aCARD11 promoted dark zone skewing along with increased cycling, AID levels, and class switch recombination. Furthermore, aCard11 GC B cells displayed increased biomass and mTORC1 signaling, suggesting a novel strategy for targeting aCARD11-driven DLBCL. While aCARD11 potently impacts GC responses, the rapid GC contraction suggests it requires collaboration with events that limit terminal differentiation to promote lymphoma.
Publisher: Elsevier BV
Date: 08-2013
Publisher: Springer New York
Date: 26-08-2010
Publisher: Springer Science and Business Media LLC
Date: 1997
Abstract: The objective of this study was to examine the effects of the intake of dietary fat upon colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. Original data records for 5,287 cases of colorectal cancer and 10,470 controls were combined. Logistic regression analysis was used to estimate odds ratios (OR) for intakes of total energy, total fat and its components, and cholesterol. Positive associations with energy intake were observed for 11 of the 13 studies. However, there was little, if any, evidence of any energy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01, 1.02, and 0.92 for quintiles of residuals of total fat intake (P trend = 0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (P trend = 0.39). The analysis suggests that, among these case-control studies, there is no energy-independent association between dietary fat intake and risk of colorectal cancer. It also suggests that simple substitution of fat by other sources of calories is unlikely to reduce meaningfully the risk of colorectal cancer.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2012
DOI: 10.1038/AJG.2012.167
Publisher: Oxford University Press (OUP)
Date: 03-03-2013
DOI: 10.1093/AJE/KWS282
Publisher: American Association for Cancer Research (AACR)
Date: 09-2006
DOI: 10.1158/1055-9965.EPI-06-0223
Abstract: Background: Colon crypt architecture and proliferation may be appropriate biomarkers for testing prevention interventions. A hypothesized mechanism for exercise-induced colon cancer risk reduction might be through alterations in colon crypt cell architecture and proliferation. Methods: Healthy, sedentary participants with a colonoscopy within the previous 3 years were recruited through gastroenterology practices and media. We randomly assigned 100 women and 102 men, ages 40 to 75 years, to a control group or a 12-month exercise intervention of moderate-to-vigorous aerobic exercise, 60 minutes per day, 6 days per week, and assessed change in number and relative position of Ki67-stained cells in colon mucosal crypts. Results: Exercisers did a mean 370 min/wk (men) and 295 min/wk (women) of exercise (seven dropped the intervention). In men, the mean height of Ki67-positive nuclei relative to total crypt height was related to amount of exercise, with changes from baseline of 0.0% (controls), +0.3% (exercisers & min/wk), −1.7% (exercisers 250-300 min/wk), and −2.4% (exercisers & min/wk Ptrend = 0.03). In male exercisers whose cardiopulmonary fitness (VO2max) increased & %, the mean height of Ki67-positive nuclei decreased by 2% versus 0.9% in other exercisers, and versus no change in controls (Ptrend = 0.05). Similar trends were observed in other proliferation markers. In women, increased amount of exercise or VO2max did not result in notable changes in proliferation markers. Conclusions: A 12-month moderate-to-vigorous intensity aerobic exercise intervention resulted in significant decreases in colon crypt cell proliferation indices in men who exercised a mean of ≥250 min/wk or whose VO2max increased by ≥5%. (Cancer Epidemiol Biomarkers Prev 2006 (9):1588–97)
Publisher: Elsevier BV
Date: 1993
Abstract: To determine population knowledge, attitudes, and personal practices regarding prevention and early detection of cancer, random population s les of 25- to 74-year-old men and women in six various-sized communities in three upper-midwestern states (N = 4,915) were administered surveys and interviews during 1987-1989. Four-fifths of respondents believed cancer to be preventable. Knowledge of warning signs/symptoms of cancer and of leading causes of cancer, however, was low. Over 95% of women had had a Papanicolaou smear and a clinical breast exam or had performed a breast self-exam 65.7% of those ages 50-65 years had had a mammogram. Among men and women ages 50-65 years, 77% had had a digital rectal exam 52.5%, a fecal occult blood test and 48.3%, a sigmoidoscopy. Conditions are favorable for an increase in mammography, including favorable attitudes toward cancer prevention, strong consensus among policy-making organizations regarding guidelines for obtaining mammograms, and high levels of adherence to these recommendations by women who have had at least their first mammogram. Challenges now include acceptance of these guidelines by physicians, mammogram affordability/availability, and demonstration of efficacious, cost-effective, and reliable colorectal rostate cancer screening tests.
Publisher: Springer Science and Business Media LLC
Date: 12-2005
DOI: 10.1038/NCPONC0359
Abstract: The earliest observations on population patterns of disease and how they might inform medical practice probably occurred during the 17th century, and they continue to the present day, with increasing relevance to nutritional and infectious diseases, and cancer and other chronic diseases. Chronic-disease methods grew out of infectious-disease epidemiology, in which both field and laboratory methods are used. In diseases where intermediate biology was not initially observable (particularly cancer), record-based and interview-based epidemiology revealed some key exposures (e.g. smoking and radiation). With measurable intermediates (e.g. blood lipids), cardiovascular epidemiology also yielded inferences on causal pathways. Important changes that are remaking the field of epidemiology and will ultimately influence all aspects of medical practice include the following: high-throughput genotyping, allowing genetic and gene-environment causes of disease to be identified high-throughput proteomics, which should allow the development of early-detection methods new tools for the measurement of exposures and a molecular basis for disease taxonomy. These new methods will allow a much better understanding of both the etiology and the intermediate stages of disease however, new methods do not obviate the necessity for good study design, especially the need to be clear on the difference between observation and experiment. The greatest opportunities to inform medical practice come from the application of new methods to large-scale human observational studies, which include genetics, environment, early-detection markers, molecular classification of outcome, and treatment data. Improved molecular classification of disease will allow smaller, focused clinical trials to be undertaken and, ultimately, the tailoring of treatment to the biological profile of patient and disease.
Publisher: Informa UK Limited
Date: 10-2012
Publisher: Springer Science and Business Media LLC
Date: 24-09-2015
Publisher: American Association for Cancer Research (AACR)
Date: 15-04-2012
DOI: 10.1158/0008-5472.CAN-11-4067
Abstract: Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case–control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene–environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal Pinteraction = 1.3 × 10−4 adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered however, our results suggest potential modification of the rs16892766 effect by vegetable consumption. Cancer Res 72(8) 2036–44. ©2012 AACR.
Publisher: Wiley
Date: 06-06-2008
DOI: 10.1002/IJC.23595
Abstract: Current literature on cancer epidemiology typically discusses etiology of cancer by cancer type. Risks of different cancer types are, however, correlated at population level and may provide etiological clues. We showed previously an unexpected very high positive correlation between breast cancer (BC) and young-adult Hodgkin disease incidence rates. In a population-based case-control study of BC, older ages at the first Epstein-Barr virus exposure, indicated by older ages at onset of infectious mononucleosis, were associated with elevated BC risk. Here we examine BC risk in association with microbial cancer (MC) risk in female populations across the world. MC cancers are cervical, liver and stomach cancers with established causal associations with human papillomaviruses, hepatitis viruses, and helicobacter pylori, respectively. We examined age-adjusted BC and MC incidence rates in 74 female populations around the world with cancer registries. Our analysis suggests that BC and MC rates are inversely associated in a special mathematical form such that the product of BC rate and MC rate is approximately constant across world female populations. A differential equation model with solutions consistent to the observed inverse association was derived. BC and MC rates were modeled as functions of an exposure level to unspecified common factors that influence the 2 rates. In conjunction with previously reported evidence, we submit a hypothesis that BC etiology may have an appreciable link with microbial exposures (and/or immunological responses to them), the lack of which, especially in early life, may elevate BC risk.
Publisher: American Association for Cancer Research (AACR)
Date: 03-2006
DOI: 10.1158/1055-9965.EPI-05-0804
Abstract: Prostacyclin synthase (PGIS) and arachidonate 5-lipoxygenase (ALOX5) are enzymes relevant to prostaglandin and leukotriene synthesis, both important pathways for colon cancer risk. We hypothesized that genetic variation altering the function of these enzymes would modify risk of colorectal polyps. In a Minnesota-based case-control study of adenomatous (n = 517) or hyperplastic (n = 192) polyps versus polyp-free controls (n = 618), we investigated the role of promoter repeat polymorphisms in PGIS and ALOX5 as well as ALOX5 −1700 G& A. Having fewer than six repeats on both PGIS alleles (& R/& R) was associated with an increased risk of adenomas compared with the 6R/6R (wild-type) genotype (OR, 1.90 95% CI, 1.09-3.30). Having more repeats (& R/≥6R) reduced risk (OR, 0.73 95% CI, 0.40-1.35 Ptrend = 0.03). In allele-based analyses, fewer repeats were associated with a modestly increased risk of adenomas and perhaps hyperplastic polyps. There were no risk differences for either the ALOX5 VNTR or −1700 G& A polymorphisms. Associations with regular use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) differed by PGIS genotype. Among in iduals with at least one wild-type allele, NSAID use was associated with a decreased risk however, those with fewer PGIS repeats (& R/& R) did not benefit (Pinteraction = 0.06). There was also evidence of an interaction between the COX-2 −765 G& C and ALOX5 −1700 G& A genotypes (Pinteraction = 0.07). The PGIS promoter polymorphism may affect risk of colorectal polyps and modify the effects of NSAID use on polyp risk. A more comprehensive investigation of genetic variability in prostaglandin synthesis in relation to risk of colorectal neoplasia and NSAID pharmacogenetics is warranted. (Cancer Epidemiol Biomarkers Prev 2006 (3):502–8)
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1999
DOI: 10.1097/00005768-199909000-00012
Abstract: Physical activity has been associated with a decreased risk for breast cancer. Mechanisms for this association may involve hormonal pathways. The Physical Activity for Total Health study is testing the effect of a 1-yr moderate intensity physical activity intervention on the endogenous sex hormone profile of postmenopausal women in a randomized controlled study. Women (N = 168) who are aged 55-75 yr, not using sex hormones, sedentary, nonsmokers, have no endocrine-related disease or cancer, and with body mass index of 25.0 or greater, are eligible. Women are recruited through mass mailings and media advertising and are randomized to either a 1-yr moderate intensity aerobic and strength training exercise program (monitored group exercise sessions plus home exercise) or a control program (stretching classes). Serum hormones to be assayed at baseline and at the end of the study include: total estrone, total estradiol, free estradiol, percent bioavailable estradiol, estrone sulfate, sex hormone binding globulin, albumin, testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, insulin, glucose, and triglycerides. Other outcome measures include: the ratio of urinary 2-hydroxyestrone: 16alpha-hydroxyestrone (an estrogen metabolite ratio that may be associated with risk for breast cancer), weight, body mass index, total fat mass, and body fat distribution (waist:hip circumference ratio, DEXA scan, and abdominal fat measured by computed tomography). This study is the first to examine the effect of change in physical activity level on sex hormones in postmenopausal women. It will provide insight into possible mechanisms through which physical activity might be associated with reduced risk of breast cancer.
Publisher: Springer Science and Business Media LLC
Date: 1996
DOI: 10.1007/BF00115644
Abstract: Several variants of SARS-CoV-2 have emerged. Those with mutations in the angiotensin-converting enzyme (ACE2) receptor binding domain (RBD) are associated with increased transmission and severity. In this study, we developed both antibody quantification and functional neutralization assays. Analyses of both COVID-19 convalescent and diagnostic cohorts strongly support the use of RBD antibody levels as an excellent surrogate to biochemical neutralization activities. Data further revealed that the s les from mRNA vaccinated in iduals had a median of 17 times higher RBD antibody levels and a similar degree of increased neutralization activities against RBD-ACE2 binding than those from natural infections. Our data showed that N501Y RBD had fivefold higher ACE2 binding than the original variant. While some antisera from naturally infected subjects had substantially reduced neutralization ability against N501Y RBD, all blood s les from vaccinated in iduals were highly effective in neutralizing it. Thus, our data indicates that mRNA vaccination may generate more neutralizing RBD antibodies than natural immunity. It further suggests a potential need to maintain high RBD antibody levels to control the more infectious SARS-CoV-2 variants.
Publisher: Elsevier BV
Date: 1982
DOI: 10.1016/0021-9681(82)90048-0
Abstract: Some extensions to simple international correlation analyses are examined with reference to beer consumption and bowel and lung cancers in 29 countries. Simple correlation of cross-sectional data for beer consumption and rectal cancer yields a coefficient of 0.77 in males and 0.75 in females. Lagged correlation analyses show a different temporal relationship between beer and colon cancer (little change over time) and rectal cancer (maximal correlation for contemporaneous, i.e. cross-sectional, data sets). Lagged correlation analysis of beer consumption and lung cancer shows a similar pattern to that for rectal cancer and beer, and markedly different from that for lung cancer and cigarettes, the former showing maximal correlation for contemporaneous data, the latter peaking 15 yr prior to date of mortality. Changes in beer consumption over time correlate with subsequent changes in rectal cancer, particularly amongst younger age groups. The sex-ratio of rectal cancer varies from around 1 in low beer consumption countries to about 1.75 in high consumption countries. The utility of these extensions to the usual simple correlation analyses is considered. The biologic plausibility of beer-bowel cancer relationships, and possible mechanisms, are discussed in the light of the findings.
Publisher: Elsevier BV
Date: 07-2012
Publisher: American Medical Association (AMA)
Date: 07-07-2015
Publisher: MDPI AG
Date: 28-09-2017
Publisher: American Association for Cancer Research (AACR)
Date: 2004
DOI: 10.1158/1055-9965.EPI-03-0097
Abstract: Methionine synthase [5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR)] is involved in folate-mediated one-carbon metabolism, a pathway known to play a role in colorectal carcinogenesis. We investigated whether the MTR D919G polymorphism was associated with risk of colorectal adenoma in a colonoscopy-based study of 513 cases and 609 controls from Minneapolis, MN. Adenoma risk appeared nonsignificantly increased among women with DG or GG genotype [adjusted odds ratio (OR) versus DD, 1.4 95% confidence interval (CI), 0.9–2.1] but not men (OR, 1.0 95% CI, 0.7–1.5). An interaction with methionine intake was observed among women, such that low versus high intake was associated with a 2.3-fold increased risk only among those with DG or GG genotype (95% CI, 1.1–4.9 P for interaction = 0.05). Similarly, risk associated with alcohol intake was not elevated among women with the DD genotype however, consumption of & g of alcohol/day versus none was associated with an increased risk among women with DG or GG genotype (adjusted OR, 2.5 95% CI, 1.4–4.4 P for interaction = 0.03). An interaction between MTR D919G and the thymidylate synthase (TS or TYMS) 3′-untranslated region polymorphism 1494del6 was also observed among women (P for interaction = 0.007). No evidence of interaction with intake of folate, vitamin B12, or vitamin B6 or with genotype at MTHFR C677T or the TS enhancer region 28-bp repeat polymorphism was seen. These findings add to what is known about the complexities of genetic variations in one-carbon-metabolizing enzymes in relation to colorectal carcinogenesis.
Publisher: American Association for Cancer Research (AACR)
Date: 05-2007
DOI: 10.1158/1055-9965.EPI-06-0701
Abstract: Prolactin is associated with an increased risk of postmenopausal breast cancer however, few modifiable factors are known to reduce prolactin concentrations. Therefore, we examined the effect of a 12-month moderate-intensity exercise intervention on serum prolactin concentrations as a secondary end point (primary end points were estrogens and androgens). We randomly assigned 173 postmenopausal women who were sedentary, overweight (body mass index & kg/m2, body fat & %), ages 50 to 75 years, and not using hormone therapy to an exercise intervention or stretching control group. The intervention was facility- and home-based (45 min, 5 days/wk moderate-intensity sports/recreational exercise). One hundred and seventy (98%) women completed the study. Prolactin concentrations were similar at baseline (P = 0.25, geometric mean exercisers = 6.9 and controls = 7.5 ng/mL). Overall, the intervention was not associated with changes in prolactin concentrations between exercisers and controls at 3 months (P = 0.46) or 12 months (P = 0.29). The intervention effect did not vary by baseline age, body mass index, parity, or change in percent body fat during the intervention. Among exercisers, there was a significant difference in prolactin concentrations by change in fitness (VO2max) between baseline and 12 months. Exercisers whose VO2max changed by & % had a 5% increase in prolactin concentrations, whereas those who increased their VO2max by 5% to 15% and & % had a 11% (P = 0.03) and 7% (P = 0.01) decrease in prolactin concentrations, respectively. Although the exercise intervention had little effect on prolactin concentrations overall, increasing physical fitness was associated with reduced prolactin concentrations among postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2007 (5):895–9)
Publisher: BMJ
Date: 24-10-2011
Publisher: BMJ
Date: 03-06-2008
Publisher: American Association for Cancer Research (AACR)
Date: 09-2020
DOI: 10.1158/1055-9965.EPI-19-1507
Abstract: Telomeres play an important role in colorectal cancer prognosis. Variation in telomere maintenance genes may be associated with survival after colorectal cancer diagnosis, but evidence is limited. In addition, possible interactions between telomere maintenance genes and prognostic factors, such as smoking and sex, also remain to be investigated. We conducted gene-wide analyses of colorectal cancer prognosis in 4,896 invasive colorectal cancer cases from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) 1,871 common variants within 13 telomere maintenance genes were included. Cox models were fit to estimate associations of these variants in idually with overall and colorectal cancer–specific survival. Likelihood ratio tests were used to test for interaction by smoking and sex. P values were adjusted using Bonferroni correction. The association between minor allele of rs7200950 (ACD) with colorectal cancer–specific survival varied significantly by smoking pack-years (corrected P = 0.049), but no significant trend was observed. By sex, minor alleles for rs2975843 (TERF1), rs75676021 (POT1), and rs74429678 (POT1) were associated with decreased overall and/or colorectal cancer–specific survival in women but not in men. Our study reported a gene-wide statistically significant interaction with sex (TERF1, POT1). Although significant interaction by smoking pack-years (ACD) was observed, there was no evidence of a dose response. Validation of these findings in other large studies and further functional annotation on these SNPs are warranted. Our study found a gene–smoking and gene–sex interaction on survival after colorectal cancer diagnosis, providing new insights into the role of genetic polymorphisms in telomere maintenance on colorectal cancer prognosis.
Publisher: Wiley
Date: 29-03-2013
DOI: 10.1111/JOIM.12062
Publisher: Informa UK Limited
Date: 03-2005
DOI: 10.1207/S15327914NC5102_5
Abstract: Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been hypothesized as being involved in colorectal cancer given its role in adipocyte development and insulin resistance. In this study we evaluated the association between the Pro12Ala (P12A) PPARgamma polymorphism and body mass index (BMI), waist-to-hip ratio (WHR), physical activity level, and energy intake and risk of colorectal cancer using data from a population-based, case-control study of colon cancer (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls). We further evaluated how the P12A PPARgamma polymorphism is associated with obesity and fat pattern in the control population. The odd ratio for PPARgamma PA or AA genotype relative to the PP genotype for colon cancer was 0.9 (95% confidence interval, CI=0.8-1.0) and for rectal cancer was 1.2 (95% CI=1.0-1.5) adjusting for race, age, and sex. P12A PPARgamma did not significantly interact with BMI, WHR, energy intake, and energy expenditure to alter risk of colon or rectal cancer. Furthermore, the P12A PPARgamma polymorphism was not associated with obesity or WHR in the control population it did not interact with energy intake or energy expenditure to alter risk of obesity or large WHR. These data do not support the hypothesis that the P12A PPARgamma polymorphism is associated with colon or rectal cancer through regulation of energy balance.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000327782
Abstract: i Background/Aims: /i Interin idual variation in aspirin (ASA) metabolism is attributed to concomitant use of drugs or alcohol, urine pH, ethnicity, sex, and genetic variants in UDP-glucuronosyltransferases (UGT). Little is known about the effects of diet. i Methods: /i We evaluated cross-sectionally whether urinary excretion of ASA and its metabolites [salicylic acid (SA), salicyluric acid (SUA) phenolic glucuronide (SUAPG), salicylic acid acyl glucuronide (SAAG) and salicylic acid phenolic glucuronide (SAPG)] differed by UGT1A6 genotype and dietary factors shown to induce UGT. Following oral treatment with 650 mg ASA, urine was collected over 8 h in 264 men and 264 women (21–45 years old). i Results: /i There were statistically significant differences in metabolites excreted between sexes and ethnicities. Men excreted more SUA women more ASA (p = 0.03), SA, SAAG and SAPG (p ≤ 0.001 for all). Compared to Caucasians, Asians excreted more ASA, SA and SAAG, and less SUA and SUAPG (p ≤ 0.03 for all) African-Americans excreted more SAAG and SAPG and less SUA (p ≤ 0.04). There was no effect of UGT1A6 genotypes. Increased ASA and decreased SUAPG excretion was observed with increased servings of vegetables (p = 0.008), specifically crucifers (p = 0.05). i Conclusion: /i Diet may influence the pharmacokinetics of ASA, but effects may be through modulation of glycine conjugation rather than glucuronidation.
Publisher: Wiley
Date: 18-03-2003
DOI: 10.1002/GCC.10189
Abstract: Pancreatic adenocarcinoma is a disease with high mortality for which chronic pancreatitis confers a markedly increased risk. We hypothesize that chromosome instability and genomic damage occur in pre-neoplastic pancreatic ductal epithelium, and that this damage may be related to oxidative stress. We used dual-color fluorescence in situ hybridization with centromere probes and locus-specific arm probes for chromosome arms 11q, 17p, and 18q to identify genomic instability in cultures of normal-appearing human pancreatic ductal epithelium from normal organ donor controls compared to patients with chronic pancreatitis or pancreatic adenocarcinoma. To examine early pancreatic tumorigenesis, we studied only normal-appearing pancreatic ductal cells adjacent to pancreatitis or carcinoma. We found that, compared to the finding in normal controls, chromosomal abnormalities are present in normal-appearing human pancreatic ductal epithelia obtained from patients with chronic pancreatitis or pancreatic adenocarcinoma. Furthermore, these chromosomal abnormalities could be induced in cultured pancreatic ductal epithelium from normal organ donors by chronic exposure to dilute hydrogen peroxide, suggesting that oxidative stress may contribute to the development of chromosomal instability in the pancreas. These results elucidate a potential mechanism linking chronic pancreatitis to pancreatic cancer and suggest that chromosomal instability may be an early event in the pathogenesis of pancreatic cancer.
Publisher: Informa UK Limited
Date: 07-2006
DOI: 10.1207/S15327914NC5501_5
Abstract: Modifiable risk factors in colorectal cancer etiology and their interactions with genetic susceptibility are of particular interest. Functional vitamin D receptor (VDR) gene polymorphisms may influence carcinogenesis through modification of cell growth, protection from oxidative stress, cell-cell matrix effects, or insulin and insulin-like growth factor pathways. We investigated interactions between foods (dairy products, red and processed meat, and whole and refined grains) and dietary patterns (sucrose-to-fiber ratio and glycemic index) associated with insulin resistance with the FokI polymorphism of the VDR gene and colon and rectal cancer risk. Data (diet, anthropometrics, and lifestyle) and DNA came from case-control studies of colon (1,698 cases and 1,861 controls) and rectal cancer (752 cases and 960 controls) in northern California, Utah, and the Twin Cities metropolitan area, Minnesota (colon cancer study only). Unconditional logistic regression models were adjusted for smoking, race, sex, age, body mass index, physical activity, energy intake, dietary fiber, and calcium. The lowest colon cancer risk was observed with the Ff/ff FokI genotypes and a low sucrose-to-fiber ratio. Rectal cancer risk decreased with greater consumption of dairy products and increased with red or processed meat consumption and the FF genotype. Modifiable dietary risk factors may be differentially important among in iduals by VDR genotype and may act through the insulin pathway to affect colon cancer risk and through fat, calcium, or other means to influence rectal cancer risk.
Publisher: Springer Science and Business Media LLC
Date: 11-06-1999
Publisher: Springer Science and Business Media LLC
Date: 03-1995
DOI: 10.1007/BF00052771
Publisher: Wiley
Date: 2001
DOI: 10.1002/IJC.1487
Abstract: Most previous studies addressing the association of body size, weight change and body fat distribution with the risk of breast cancer were conducted in Western societies with a high proportion of overweight people. It remains unclear whether the dose-response relation observed in earlier studies can be extended to women with "normal" weight based on prevailing Western standards. To address this issue, we analyzed data from a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews and anthropometric measurements were completed for 1,459 women newly diagnosed with breast cancer from 25 to 64 years of age and 1,556 controls frequency-matched to cases on age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI) related to anthropometric variables and self-reported body weight. Currently measured weight, body mass index [BMI: weight (kg)/height(m)(2)] or height was each found to be positively related to risk of postmenopausal breast cancer in a dose-response manner, with ORs (95% CI) being 2.0 (1.4-3.0), 2.0 (1.2-3.2) or 1.7 (1.2-2.5), respectively, for the highest category of weight, BMI or height compared to the lowest category of these variables. These variables were unrelated to premenopausal breast cancer risk. Reported weight at ages >40 years and weight gain after age 20 were more predictive for postmenopausal breast cancer than weight at an earlier age. After adjustment for BMI, waist-to-hip ratio was related to an increased risk of premenopausal [OR = 1.7 (1.3-2.3) for the highest category compared to the lowest category] but not postmenopausal breast cancer. This study suggests that, even in a relatively thin Chinese population, weight gain and height are related to an increased risk of postmenopausal breast cancer, while central fat distribution was associated with premenopausal breast cancer. General weight control may be an effective measurement for breast cancer prevention.
Publisher: Elsevier BV
Date: 10-2015
Publisher: American Association for Cancer Research (AACR)
Date: 02-2004
DOI: 10.1158/1055-9965.EPI-03-0083
Abstract: 5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, erting metabolites toward methylation reactions or nucleotide synthesis. Using data from an incident case-control study (1608 cases and 1972 controls) we investigated two polymorphisms in the MTHFR gene, C677T and A1298C, and their associations with risk of colon cancer. All of the combined genotypes were evaluated separately, and the 1298AA/677CC (wild-type/wild-type) group was considered the reference group. Among both men and women, the 677TT/1298AA (variant/wild-type) genotype was associated with a small reduction in risk [men: odds ratio (OR), 0.7, 95% confidence interval (CI), 0.5–1.0 women: OR, 0.8, 95% CI, 0.5–1.2]. However, the 677CC/1298CC (wild-type/variant) genotype was associated with a statistically significant lower risk among women (OR, 0.6 95% CI, 0.4–0.9) but not men. When the polymorphisms were considered in idually, for A1298C a significant risk reduction associated with the homozygous variant CC genotype was seen among women only (OR, 0.6 95% CI, 0.5–0.9), and nonstatistically significant reduced risks were observed for the variant 677 TT genotypes among both men and women. Stratification by nutrient intakes showed inverse associations with higher intakes of folate, vitamin B2, B6, B12, and methionine among women with the MTHFR 677CC/1298AA genotypes, but not those with 677TT/1298AA. We observed opposite risk trends for both MTHFR variants, depending on whether women used hormone-replacement therapy or not (P for interaction = & .01). In summary, this study supports recent findings that the MTHFR A1298C polymorphism may be a predictor of colon cancer risk and have functional relevance. The possible interaction with hormone-replacement therapy warrants additional investigation.
Publisher: Wiley
Date: 2000
DOI: 10.1002/1097-0215(20000715)87:2<295::AID-IJC23>3.0.CO;2-7
Abstract: The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence, we analyzed data from the Shanghai Breast Cancer Study, a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews were completed for 1,459 women newly diagnosed with breast cancer between ages 25 and 64 and for 1,556 controls frequency-matched to cases by age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) related to menstrual and reproductive factors. Earlier menarcheal age, nulliparity, and later age at first live birth were associated with increased risk of breast cancer among both pre- and post-menopausal women, while never having breast-fed and later age at menopause were associated with elevated risk only among post-menopausal women. Among controls, 32% of younger women ( 40 years) reported starting menarche at age of 13 or younger, and this factor contributed to 44% of cases diagnosed among younger women and 26% to 28% of cases in older women. Older age at first live birth or at menopause explained a considerable portion of cases diagnosed in older, but not younger, women. Our study suggests that the changes in menstrual and reproductive patterns among women in Shanghai have contributed to the recent increase in breast cancer incidence, particularly among younger women.
Publisher: Elsevier BV
Date: 03-1989
DOI: 10.1016/0165-7992(89)90126-7
Abstract: The fruit bat species Rousettus aegyptiacus was identified as a potential reservoir for the highly pathogenic filovirus Marburg virus. To establish a basis for a molecular understanding of the biology of filoviruses in the reservoir host, we have adapted a set of molecular tools for investigation of filovirus replication in a recently developed cell line, R06E, derived from the species Rousettus aegyptiacus. Upon infection with Ebola or Marburg viruses, R06E cells produced viral titers comparable to VeroE6 cells, as shown by TCID(50) analysis. Electron microscopic analysis of infected cells revealed morphological signs of filovirus infection as described for human- and monkey-derived cell lines. Using R06E cells, we detected an unusually high amount of intracellular viral proteins, which correlated with the accumulation of high numbers of filoviral nucleocapsids in the cytoplasm. We established protocols to produce Marburg infectious virus-like particles from R06E cells, which were then used to infect naïve target cells to investigate primary transcription. This was not possible with other cell lines previously tested. Moreover, we established protocols to reliably rescue recombinant Marburg viruses from R06E cells. These data indicated that R06E cells are highly suitable to investigate the biology of filoviruses in cells derived from their presumed reservoir.
Publisher: American Association for Cancer Research (AACR)
Date: 02-2015
DOI: 10.1158/1055-9965.EPI-14-1327
Abstract: Consideration is given to the idea that the nutritional epidemiology of cancer is dead, as some in the media have claimed. The basis for the claim does not lie in science nor has anyone with relevant knowledge made such a statement—although that, too, has been claimed. Evidence is adduced for the importance of past achievements of nutritional epidemiology. Attention is similarly drawn to recent contributions. In particular, I note the state of play of cancer and plant foods, fat and breast cancer, meat and cancer, vegetarians, intervention studies, migrant studies, and westernization of diet and lifestyle. Some next steps and some currently important questions are outlined. Cancer Epidemiol Biomarkers Prev 24(2) 323–30. ©2014 AACR.
Publisher: Public Library of Science (PLoS)
Date: 31-05-2012
Publisher: Elsevier BV
Date: 02-1997
DOI: 10.1016/S1047-2797(96)00129-9
Abstract: It has been suggested that performing physical activity for at least 30 min on most days of the week will improve health. The purpose of this study was to assess the association between physical activity and colon cancer as it relates to this public health recommendation. A large population-based case-control study of colon cancer was conducted. Study participants came from three areas of the United States: Northern California, Utah, and the Twin Cities Metropolitan Area in Minnesota. Long-term involvement in high levels of activity, equivalent to > or = 60 min of vigorous activity per session, was associated with decreased risk (odds ration [OR], 0.68 95% confidence interval [CI] 0.52-0.87). The amount of time involved in the activity appeared to have a greater impact than the number of days per week that activities were performed. Those reporting the highest level of activity, as defined by both duration and vigorous intensity, were at the lowest risk (OR, 0.62 95% CI, 0.52-0.75) relative to those who were sedentary associations did not differ by age at diagnosis, site of the tumor within the colon, or sex. The inverse association between colon cancer and long-term vigorous leisure-time activity was slightly stronger among those without a family history of colorectal cancer than among those with a family history of colorectal cancer. From these data we estimate that 13% of colon cancer could be attributed to lack of vigorous leisure-time activity in the population we estimate that 4.3 cases of colon cancer/100,000 population are prevented each year because people are involved in vigorous leisure-time physical activity. Data from this study suggest that a high level of vigorous leisure-time activity performed over the past 20 years was important in reducing colon cancer risk the greatest inverse association was observed when activities were performed for longer periods of time per session for the past 20 years. These and other data indicate that it is important to identify ways to facilitate an increase in leisure-time physical activity within the population.
Publisher: Springer Science and Business Media LLC
Date: 09-1994
DOI: 10.1007/BF01694752
Publisher: American Medical Association (AMA)
Date: 28-05-2008
Publisher: Wiley
Date: 27-04-2011
DOI: 10.1002/IJC.26047
Publisher: Springer Science and Business Media LLC
Date: 09-1991
DOI: 10.1007/BF00051672
Publisher: American Association for Cancer Research (AACR)
Date: 11-2012
DOI: 10.1158/1055-9965.EPI-12-0692
Abstract: Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association. Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors. Results: Current smokers [OR, 1.26 95% confidence interval (CI), 1.11–1.43] and former smokers (OR, 1.18 95% CI, 1.09–1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI relative excess risk due to interaction (RERI]), 0.15 95% CI, −0.01 to 0.31 P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16 95% CI, 0.01–0.30 P = 0.04). Conclusion: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking. Impact: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology. Cancer Epidemiol Biomarkers Prev 21(11) 1974–85. ©2012 AACR.
Publisher: Oxford University Press (OUP)
Date: 04-2015
DOI: 10.1093/IJE/DYV082
Publisher: Springer Science and Business Media LLC
Date: 04-01-2011
Publisher: American Association for Cancer Research (AACR)
Date: 10-2012
DOI: 10.1158/1055-9965.EPI-12-0674
Abstract: Background:BRAF mutations in colorectal cancer (CRC) are disproportionately observed in tumors exhibiting microsatellite instability (MSI) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear. Methods: We evaluated the association between the BRAF c.1799T& A (p.V600E) mutation and survival in in iduals with incident invasive CRC diagnosed between 1997 and 2007 in Western Washington State. Tumor specimens were tested for this BRAF mutation and MSI status. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the association between BRAF mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumor site, stage, and MSI status. Results: Among 1,980 cases tested, 12% were BRAF c.1799T& A (p.V600E) mutation–positive (n = 247). BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43 95% CI, 1.05–1.95). This association was limited to cases diagnosed at ages & (HR, 3.06 95% CI, 1.70–5.52) and was not evident in cases with MSI-high tumors (HR, 0.94 95% CI, 0.44–2.03). Associations with overall survival were similar. Conclusions: Our results show that the prevalence of BRAF mutations in CRC differs by patient and tumor characteristics and suggest that the association between BRAF status and CRC survival may differ by some of these factors. Impact: The presence of a BRAF c.1799T& A (p.V600E) mutation is associated with significantly poorer prognosis after CRC diagnosis among subgroups of patients. Cancer Epidemiol Biomarkers Prev 21(10) 1792–8. ©2012 AACR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2009
Publisher: Oxford University Press (OUP)
Date: 08-10-2009
DOI: 10.1093/BIB/BBN042
Publisher: American Association for Cancer Research (AACR)
Date: 15-11-2004
DOI: 10.1158/1078-0432.CCR-04-1057
Abstract: Purpose: Methylenetetrahydrofolate reductase (MTHFR) directs intracellular folate toward homocysteine metabolism and away from nucleotide synthesis. Two common MTHFR polymorphisms, C677T and A1298C, are associated with reduced enzyme activity. We evaluated the association of these polymorphisms with risk of relapse and bcr-abl mRNA transcript detection among 336 Caucasian patients who underwent allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia. Experimental Design: Data on the transplant course and folate-related exposures were abstracted from medical records. MTHFR C677T and A1298C genotypes were determined using polymerase chain reaction/restriction fragment length polymorphism and TaqMan assays. Qualitative bcr-abl mRNA testing was conducted using a two-step reverse transcription-polymerase chain reaction assay. Cox regression analysis was used to assess the association between MTHFR genotypes and time to relapse and bcr-abl mRNA detection. Results: A statistically significant decreased risk of relapse was observed in patients with the variant A1298C genotype [1298AC, hazard ratio (HR) = 0.48 and 95% confidence interval (CI) = 0.26–0.88 1298CC, HR = 0.28 and 95% CI = 0.09–0.84 P-trend & 0.01). For the joint C677T/A1298C genotype, variant genotypes were associated with a decreased risk of relapse when compared with the wild-type 677CC/1298AA genotype. This risk was lowest for the 677CC/1298CC genotype (HR, 0.23 95% CI, 0.08–0.72). MTHFR genotypes were not associated with bcr-abl transcript detection. Conclusions: These findings suggest that in iduals with the 677CC/1298AA genotype are at higher risk of relapse after hematopoietic cell transplantation and that the balance of intracellular folate metabolites available for nucleotide synthesis (regulated by the relative activity of the MTHFR enzyme) may affect the progression from bcr-abl positivity to clinical relapse.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1999
DOI: 10.1111/J.1572-0241.1999.00769.X
Abstract: The relationship between cholecystectomy and the occurrence of subsequent colon cancer has been controversial. Using data collected as part of an incident case-control study of colon cancer conducted in northern California, Minnesota, and Utah, we evaluated this association. Participants were between 30 and 79 yr of age and had a first primary colon cancer diagnosed between October 1, 1991 and September 30, 1994. Analyses were adjusted for age, gender, family history of colorectal cancer, body mass index, dietary energy and fiber intake, use of aspirin or nonsteroidal antiinflammatory drugs, and long-term leisure-time vigorous physical activity. A weak positive association between cholecystectomy and proximal colon cancer (odds ratio [OR] and 95% confidence interval [CI] 1.3 [1.0-1.6]) was observed. This was counterbalanced by a weak, nonsignificant negative association (OR 0.8, 95% CI 0.6-1.1) with distal colon cancer leading to no overall association (OR 1.0, 95% CI 0.9-1.2). The association between colon cancer and cholecystectomy did not differ by gender or race, but it did differ by study area, with most of the increased association being attributed to the Minnesota population. The elevated risk of proximal colon cancer increased after cholecystectomy but disappeared after 14 years. Our results suggest that cholecystectomy or the underlying gallstone disease that prompts it may be related weakly to the risk of subsequent proximal colon cancer. However, the association may differ by geographic area of the country, and may be artifactual at least in part.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2006
Publisher: Wiley
Date: 10-06-2015
DOI: 10.1002/GEPI.21908
Publisher: American Association for Cancer Research (AACR)
Date: 08-2023
DOI: 10.1158/0008-5472.C.6769316
Abstract: Abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 ( i FMN1/GREM1 /i ) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the i FMN1/GREM1 /i gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies. /
Publisher: American Association for Cancer Research (AACR)
Date: 12-2007
DOI: 10.1158/1055-9965.EPI-07-0467
Abstract: Obesity has been shown to be associated with an increased risk of both colorectal cancer and adenomatous polyps. One mechanism underlying this relationship may involve the growth-promoting effects of the circulating hormones associated with obesity, such as leptin. We conducted a gastroenterology clinic-based, case-control study to evaluate the relationship between circulating leptin concentrations and colorectal adenoma risk in addition, we evaluated the relationship between leptin receptor polymorphisms and adenoma risk. In iduals with adenomas (n = 157) and colonoscopy-negative controls (n = 191), who had a clinically indicated colonoscopy, were recruited from a large health maintenance organization in the Seattle metropolitan area from 1999 to 2003. Odds ratios and 95% confidence intervals were obtained using logistic regression, adjusting for age at diagnosis, body mass index, family history of colorectal cancer, smoking history, nonsteroidal anti-inflammatory drug use, physical activity, and, among women, menopausal status and postmenopausal hormone use. Among men, those in the highest tertile of leptin concentrations had a 3.3-fold (95% confidence interval, 1.2-8.7) increased adenoma risk compared with those in the lowest tertile (P trend = 0.01). There were no associations between leptin concentrations and adenoma risk in women. There were no associations of leptin receptor genotypes or haplotypes and adenoma risk. The results of this study suggest that, in men, leptin may be associated with risk of colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2007 (12):2697–703)
Publisher: Oxford University Press (OUP)
Date: 21-07-2010
DOI: 10.1093/JNCI/DJQ201
Publisher: Oxford University Press (OUP)
Date: 03-02-2010
DOI: 10.1093/JNCI/DJP473
Publisher: American Association for Cancer Research (AACR)
Date: 07-2015
DOI: 10.1158/1055-9965.EPI-14-1309
Abstract: Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer. Methods: We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study–identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis. Results: In iduals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk [per weighted allele OR, 1.31 95% confidence interval (CI), 1.10–1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m2, 1.50 95% CI, 1.13–2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m2, 1.82 95% CI, 1.26–2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m2, 1.18 95% CI, 0.73–1.92). Conclusions: High BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation. Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 24(7) 1024–31. ©2015 AACR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2006
DOI: 10.1111/J.1572-0241.2006.00551.X
Abstract: Mutations in the mismatch repair (MMR) enzymes hMLH1 and hMSH6 are known causes of hereditary nonpolyposis colorectal cancer and act by inducing a mutator phenotype characterized by microsatellite instability. The aim of our study was to determine if polymorphisms in the DNA MMR genes hMLH1 and hMSH6 are associated with an increased risk of colorectal polyps, and to evaluate interactions with exposures known to cause DNA damage. In a Minnesota-based case-control study of in iduals with adenomas (N=401), hyperplastic polyps (N=195), or both adenomas and hyperplastic polyps (N=123) versus polyp-free controls (N=624), we investigated the role of hMLH1-93G>A, hMLH1 I219V, and hMSH6 G39E polymorphisms in increasing the risk of colorectal polyps. Polytomous multivariate logistic regression analysis was used, adjusting for age, sex, body mass index, postmenopausal hormone use, aspirin use, and NSAID use. Overall, no evidence of an association between any of the three polymorphisms or hMLH1 haplotypes and colorectal polyps was observed. However, risk associated with the hMLH1-93A variant differed by smoking: smoking-associated risks were stronger among those with variant -93AA or -93AG genotypes, showing a twofold greater risk of adenoma with >25 pack-years of smoking compared with nonsmokers, and a corresponding eightfold greater risk of hyperplastic polyps (genotype smoking: p-interaction=0.02 for hyperplastic polyps and p-interaction=0.08 for adenomas). These data are consistent with the observation that smoking is associated with MMR in colorectal neoplasia and suggest that the risk increase with smoking may differ by hMLH1-93G>A genotype.
Publisher: Wiley
Date: 28-03-2014
DOI: 10.1002/GCC.22167
Publisher: Springer Science and Business Media LLC
Date: 08-02-2011
Publisher: Wiley
Date: 15-07-1995
DOI: 10.1002/1097-0142(19950715)76:2<275::AID-CNCR2820760218>3.0.CO;2-6
Abstract: The authors sought to determine whether prediagnosis obesity, body-fat distribution, and dietary intake of fats, antioxidants, and fiber may be related to survival after the diagnosis of breast cancer. The mortality rates of 698 postmenopausal patients with unilateral breast cancer in a large cohort study were analyzed. Body-mass index, waist-to-hip ratio, and food-frequency data were collected by questionnaire within 6 years before breast cancer was diagnosed. Adjusted for age, women in the highest tertile of body mass index had a 1.9-fold higher risk (95% confidence interval = 1.0-3.7) of dying after breast cancer than those in the lowest tertile adjusted for other prognostic variables (age, smoking, education level, extent of breast cancer, and tumor size), this relative risk was 1.5 (95% CI = 0.7 to 2.9). Waist-to-hip ratio was not related to risk of dying nor was intake of fiber or several dietary antioxidants. Independent of other prognostic variables, risk of death after breast cancer was statistically significantly elevated, with a relative risk greater than 2.0 for the highest tertiles of total fat, saturated fat, and monounsaturated fat intake, expressed as grams per day. An adjustment for energy intake, which also was associated positively with fatality, weakened these associations somewhat. Although clinical trials are required, these findings support the hypothesis that a high fat intake is associated with reduced survival of postmenopausal women with breast cancer and suggest that women with breast cancer should consider limiting their intake of fat.
Publisher: Wiley
Date: 12-02-2013
DOI: 10.1002/GCC.22042
Publisher: Springer Science and Business Media LLC
Date: 26-04-2005
Publisher: American Association for Cancer Research (AACR)
Date: 02-2010
DOI: 10.1158/1055-9965.EPI-09-0662
Abstract: Epidemiologic evidence supports a role for vitamin D in colorectal cancer (CRC) risk. Variants in vitamin D–related genes might modify the association between vitamin D levels and CRC risk. In this analysis, we did a comprehensive evaluation of common variants in the vitamin D receptor (VDR) and the vitamin D–binding protein (GC group-specific component) genes using a population-based case–unaffected sibling control design that included 1,750 sibships recruited into the Colon Cancer Family Registry. We also evaluated whether any associations differed by calcium supplement use, family history of CRC, or tumor characteristics. Heterogeneity by calcium and vitamin D intake was evaluated for a subset of 585 cases and 837 sibling controls who completed a detailed food frequency questionnaire. Age- and sex-adjusted associations were estimated using conditional logistic regression. Overall, we did not find evidence for an association between any single-nucleotide polymorphism (SNP) in VDR or GC and risk for CRC (range of unadjusted P values 0.01-0.98 for VDR and 0.07-0.95 for GC). None of these associations was significant after adjustment for multiple comparisons. We also found no evidence that calcium or vitamin D intake (food and supplement) from the food frequency questionnaire modified the association estimates between VDR and GC SNPs and CRC. We did observe associations between SNPs in GC and microsatellite unstable CRC, although these results should be confirmed in additional studies. Overall, our results do not provide evidence for a role of common genetic variants in VDR or GC in susceptibility to CRC. Cancer Epidemiol Biomarkers Prev 19(2) 525–36
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-07-2005
Abstract: Anecdotal reports suggest that the volume of services offered to in iduals concerned with hereditary cancer risk has increased substantially in recent years. As a follow-up to our 1993 survey, we sought to determine how the scope and volume of genetic services has changed between 1993 and 2002. We surveyed the 61 National Cancer Institute–designated cancer centers in operation in 2002 using an updated version of the questionnaire from 1993. Analysis included frequencies and summary statistics. The majority of cancer centers responding (46 of 56 centers 82.1%) provided some genetic services for evaluation of familial cancer, which is a higher proportion than in 1993 (50% P .01). Almost all centers (42 of 46 centers 91.3%) provided services not only to cancer patients and their families, but also to in iduals concerned with risk, which is a change (P = .01) from 1993, when 64.7% of centers offered such services. In addition, increases have been found for most other measures of services rendered for familial genetic services. As public awareness of cancer susceptibility genes has grown markedly in recent years, the demand has also grown for genetic services to assess familial cancer risk. Major deleterious genetic mutations are rare, and much of the current research in genetic variation focuses on higher prevalence variants that carry lower risks. This may suggest that testing for mutations will move from genetics clinics to primary care and specialty practices. Thus, it is unclear whether the scope and volume of cancer center genetics services will continue to grow as rapidly as they have over the last decade.
Publisher: Wiley
Date: 1992
Abstract: Data on 337 lung cancer families were analyzed to determine if known cohort differences in parental cigarette consumption influence parameters from a segregation analysis. Previous results suggested that, after allowing for an in idual's pack-years of tobacco exposure, Mendelian codominant inheritance of an allele that produced an earlier age of onset provided a good fit to the data. In the present study, the data were split into two groups of families: probands age 60 and over (born before WWI) and probands younger than age 60. This partition of the data by age of the proband was done to separate families in which there were parents who were less likely to smoke from those with parents more likely to smoke--predicated on the known increase of smoking prevalence after World War I. For the younger proband families (those with parents more likely to smoke), only Mendelian codominant inheritance adequately fit the data. The hypotheses of no major type, environmental transmission, and Mendelian dominant or recessive inheritance were rejected. In contrast to our earlier findings, the estimate of population susceptibility increased from 28% in the total data to 60% in this subset. In the older proband families (those with parents less likely to smoke), the no major type and environmental hypotheses were rejected further, none of the Mendelian models could be distinguished. Our results demonstrate that cohort differences, probably in exposure to tobacco, can confound parameters of a segregation analysis, and suggest that the genetic component of lung cancer may be greater than previously estimated. It further suggests that susceptibility to lung cancer occurs as a function of susceptibility to the effects of tobacco smoking.
Publisher: Springer Science and Business Media LLC
Date: 07-1993
DOI: 10.1007/BF00051334
Publisher: Bioscientifica
Date: 09-07-2008
DOI: 10.1677/JOE-07-0569
Abstract: Experimental studies and case reports suggest a multifunctional role of leptin in immune function. However, clinical studies of leptin in healthy in iduals with a comprehensive assessment of immunity are lacking. This study investigated associations between serum leptin concentrations and multiple biomarkers of cellular immunity and inflammation among 114 healthy postmenopausal, overweight, or obese women. Leptin was measured by RIA. C-reactive protein (CRP) and serum amyloid A (SAA) were measured by nephelometry. Flow cytometry was used to measure natural killer (NK) cell cytotoxicity and to enumerate and phenotype lymphocyte subsets. T-lymphocyte proliferation was assessed in response to phytohemagluttinin, as well as to anti-CD3 antibodies by the flow cytometric cell ision tracking method. Multiple linear regression analysis with adjustment for confounding factors and log transformation, where appropriate, was used. Serum leptin concentrations were positively associated with serum CRP, SAA, and interleukin 6 (IL6) ( P .0001, P =0.01, and P =0.04 respectively), more strongly among women with a body mass index (BMI) kg/m 2 . The associations were attenuated after adjustment for measured body composition, yet remained significant for CRP and SAA. No statistically significant associations were observed between leptin and NK cytotoxicity, lymphocyte subpopulations, or T-lymphocyte proliferation. This study fills an important gap in knowledge about the relationship between leptin concentrations and immune function in healthy in iduals. Findings support an association between serum leptin and the inflammatory proteins CRP and SAA, which appears to be mediated only partly by adipose tissue. Our study does not support a link between leptin and other immune parameters among overweight or obese, but otherwise healthy postmenopausal women, perhaps because such effects are only present at low or deficient leptin concentrations.
Publisher: Springer Science and Business Media LLC
Date: 11-2005
DOI: 10.1007/S10552-005-0330-6
Abstract: Chinese women residing in Asia and Hawaii have low consumption of tobacco but a high incidence of lung cancer. To explore this question further, we conducted a study of lung cancer among Chinese women residing in mainland US. Using data from NCI's SEER program, we identified residents of Los Angeles County, the San Francisco Metropolitan Area, and the Seattle-Puget Sound Area who were 50 years or older, diagnosed with cancer of the lung or bronchus in 1999-2001, with race specified as non-Hispanic white (n = 18,493), Chinese (n = 853), Filipino (n = 615), or Japanese (n = 282). The sex-specific observed number of lung cancer cases among each Asian sub-group was compared to the expected number of lung cancer cases for each Asian sub-group. The expected number was determined by multiplying the age-, sex-, and geographic area-adjusted incidence rates for non-Hispanic whites by the age- and sex-specific ratio of percentage of current smokers in each Asian sub-group to whites in 1990, and then by the size of the respective Asian populations. Chinese women had a four-fold increased risk of lung cancer, and Filipino women a two-fold increased risk, compared to that expected based on rates in US non-Hispanic whites with a similar proportion of cigarette smokers. Lung cancer among Chinese, Filipino, and Japanese males, as well as Japanese females, did not deviate from expected risk. Among Chinese women, the increased risk was largely restricted to adenocarcinoma and large cell undifferentiated carcinoma. Chinese female residents of the western US mainland have a much higher risk of lung cancer than would be predicted from their tobacco use patterns, just as they do in Asia.
Publisher: American Association for Cancer Research (AACR)
Date: 07-2015
DOI: 10.1158/1055-9965.EPI-15-0039
Abstract: Background: Physical activity is associated with a lower incidence of colorectal cancer however, the relationship of physical activity with colorectal cancer survival is not yet clear. We evaluated the association between prediagnostic physical activity and colorectal cancer survival, overall and accounting for tumor markers associated with colorectal cancer survival: BRAF and KRAS mutation status and microsatellite instability (MSI) status. Methods: Participants were 20- to 74-year-old colorectal cancer patients diagnosed between 1998 and 2007 from the population-based Seattle Colon Cancer Family Registry (S-CCFR). Self-reported physical activity in the years preceding colorectal cancer diagnosis was summarized as average metabolic equivalent task hours per week (MET-h/wk n = 1,309). Somatic BRAF and KRAS mutations and MSI status were evaluated on a subset of patients (n = 1043). Cox regression was used to estimate HRs and 95% confidence intervals (CI) for overall and disease-specific survival after adjusting for relevant confounders. Stratified analyses were conducted across categories of BRAF, KRAS, and MSI, as well as tumor stage and site. Results: Higher prediagnostic recreational physical activity was associated with significantly more favorable overall survival (HR for highest vs. lowest category, 0.70 95% CI, 0.52–0.96) associations were similar for colorectal cancer–specific survival. Results consistently indicated a favorable association with physical activity across strata defined by tumor characteristics. Conclusion: In iduals who were physically active before colorectal cancer diagnosis experienced better survival than those who were inactive or minimally active. Impact: Our results support existing physical activity recommendations for colorectal cancer patients and suggest that the beneficial effect of activity is not specific to a particular molecular phenotype of colorectal cancer. Cancer Epidemiol Biomarkers Prev 24(7) 1130–7. ©2015 AACR.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2020
DOI: 10.1038/S41467-020-14389-8
Abstract: Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies however, it is unknown if these associations are causal or confounded. In two-s le Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER +ve ) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.
Publisher: American Association for Cancer Research (AACR)
Date: 07-2013
DOI: 10.1158/1055-9965.EPI-12-1226
Abstract: Background: Colorectal cancer (CRC) in densely affected families without Lynch Syndrome may be due to mutations in undiscovered genetic loci. Familial linkage analyses have yielded disparate results the use of exome sequencing in coding regions may identify novel segregating variants. Methods: We completed exome sequencing on 40 affected cases from 16 multicase pedigrees to identify novel loci. Variants shared among all sequenced cases within each family were identified and filtered to exclude common variants and single-nucleotide variants (SNV) predicted to be benign. Results: We identified 32 nonsense or splice-site SNVs, 375 missense SNVs, 1,394 synonymous or noncoding SNVs, and 50 indels in the 16 families. Of particular interest are two validated and replicated missense variants in CENPE and KIF23, which are both located within previously reported CRC linkage regions, on chromosomes 1 and 15, respectively. Conclusions: Whole-exome sequencing identified DNA variants in multiple genes. Additional sequencing of these genes in additional s les will further elucidate the role of variants in these regions in CRC susceptibility. Impact: Exome sequencing of familial CRC cases can identify novel rare variants that may influence disease risk. Cancer Epidemiol Biomarkers Prev 22(7) 1239–51. ©2013 AACR.
Publisher: Elsevier BV
Date: 09-1992
DOI: 10.1016/1047-2797(92)90003-9
Abstract: There are data to suggest a relationship between alcohol consumption, particularly beer, and lung cancer. This hypothesis was tested on data from a cohort of 41,837 Iowa women aged 55 to 69 years. Women were recruited by mail and provided information on alcohol and tobacco use, physical activity, and education. Compared to a randomly selected group of women without lung cancer (n = 1900), those with lung cancer (n = 109) consumed more alcohol (measured on the Willett food frequency questionnaire) (10.2 versus 3.6 g/d P = 0.001). The difference was accounted for largely by differences in beer consumption (3.5 versus 0.6 glass/wk P = 0.003). Liquor consumption by patients was about double that by control subjects (1.7 versus 0.8 glass/wk P = 0.063). Wine consumption was low and did not differ between those with and those without lung cancer. The relationship between beer consumption and lung cancer risk appeared U-shaped. After adjusting for the other variables (including six categories of pack-years of smoking), beer consumption remained a significant predictor of lung cancer risk. Those drinking 1 or more beers per week had an odds ratio of 2.0 (95% confidence interval, 1.02 to 3.80) compared with those consuming less than 1 glass per week. There was no evidence of interaction with smoking. The association of beer with lung cancer does not appear to be explained solely by confounding with cigarette smoking, although that remains by far the single strongest predictor of risk.
Publisher: Oxford University Press (OUP)
Date: 04-06-2008
DOI: 10.1093/HMG/DDN166
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 10-06-2011
Publisher: Oxford University Press (OUP)
Date: 15-06-2002
Abstract: Although high vegetable intakes have been associated with a lower risk of colorectal cancer, this relation is less well established for the precursor lesions, adenomatous polyps. With a case-control design involving adenomatous polyp cases (n = 564), colonoscopy-negative controls who were polyp free at colonoscopy (n = 682), and community controls (n = 535), this 1991-1994 Minnesota Cancer Prevention Research Unit study investigated the relation between fruit and vegetable consumption and first incident adenomatous polyps. Dietary intake was assessed using a food frequency questionnaire. For women, adenoma risk was approximately halved in the highest versus lowest quintile of juice consumption (cases vs. colonoscopy-negative controls: odds ratio (OR) = 0.50, 95% confidence interval (CI): 0.27, 0.92 cases vs. community controls: OR = 0.56, 95% CI: 0.30, 1.06). The association was stronger for adenomas with moderate or severe dysplasia compared with mild dysplasia. Juice was not associated with adenoma risk in men. The results for fruits, vegetables, total fruits and vegetables, green leafy vegetables, and several botanically and phytochemically defined subgroups generally were not statistically significant. Because elevated vegetable consumption has been associated with a lower risk of colorectal cancer, vegetables may have a stronger role in preventing the progression of adenomas to carcinomas rather than in preventing the initial appearance of adenomas.
Publisher: Oxford University Press (OUP)
Date: 21-02-2014
DOI: 10.1093/HMG/DDU087
Publisher: Elsevier BV
Date: 04-2013
Publisher: American Association for Cancer Research (AACR)
Date: 15-01-2013
DOI: 10.1158/0008-5472.CAN-12-2484
Abstract: Loss of estrogen receptor β (ERβ) expression in the gut is associated with colorectal cancer (CRC) initiation and progression. Germline single-nucleotide polymorphisms (SNP) in genes for the sex-steroid hormone receptors are not strongly associated with CRC risk however, these SNPs have not previously been evaluated in relation to survival after diagnosis. We enrolled 729 women, ages 50 to 74, diagnosed with invasive CRC between 1997 and 2002 in 13 counties covered by the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer registry. Participants provided germline DNA. We selected 99 tag-SNPs for the androgen receptor (AR), ERα (ESR1), ERβ (ESR2), and progesterone receptor (PGR) genes. Mortality outcomes were ascertained from the National Death Index. During a median of 6.6 years of follow-up, 244 deaths occurred (161 from CRC). We identified 20 SNPs (12 of ESR2 and 8 of PGR) for replication in 1,729 women diagnosed with incident invasive CRC (555 deaths 405 from CRC) from three prospective cohort studies that participate in the Genetics and Epidemiology of Colorectal Cancer Consortium. Three correlated SNPs in the promoter of ESR2 (rs2987983, rs3020443, and rs2978381) were statistically significant predictors of CRC-specific and overall survival. Minor alleles of each were associated with improved survival [for rs2987983, CRC-specific HR, 0.77 95% confidence interval (CI), 0.60–0.99 in the initial study, and HR, 0.79 CI, 0.64–0.98 in replication]. No associations were noted for SNPs of AR, ESR1, or PGR. SNPs in the promoter of ESR2 may be important to pathways related to the association between ERβ and tumor progression and metastasis. Cancer Res 73(2) 767–75. ©2012 AACR.
Publisher: Wiley
Date: 24-08-2011
DOI: 10.1002/GCC.20913
Publisher: American Association for Cancer Research (AACR)
Date: 07-2008
DOI: 10.1158/1055-9965.EPI-07-2660
Abstract: Background: Fruit and vegetable (F& V) intake may lower the risk of some cancers. One hypothesized, but understudied, chemopreventive mechanism is that plant food constituents inhibit β-glucuronidase, an acid hydrolase that deconjugates glucuronides. Methods: We conducted a crossover feeding trial in 63 healthy women and men ages 20 to 40 years to examine the effect of diet on serum β-glucuronidase activity. Participants were randomized to two 2-week experimental diets with an intervening washout period: a diet high in selected citrus fruit, crucifers, and soy (F& V) and a diet devoid of fruits, vegetables, and soy (basal). Serum β-glucuronidase activity was measured during the preintervention, F& V, and basal periods. Linear mixed models were used to obtain effect estimates and 95% confidence intervals (95% CI). Results: We observed statistically significantly higher β-glucuronidase activity during the F& V than the basal diet (ratio, F& V versus basal diet, 1.09 95% CI, 1.05-1.13 P & 0.01). These results were probably due to decreased β-glucuronidase activity during the basal diet (ratio, basal period versus preintervention, 0.93 95% CI, 0.87-0.98 P = 0.01) rather than increased enzyme activity during the F& V diet (ratio, F& V period versus preintervention, 1.01 95% CI, 0.96-1.06 P = 0.64). Response to the experimental diet did not differ by sex (Pinteraction = 0.30), but there was a suggestion of a short-term diet effect at 8 versus 15 days (Pinteraction = 0.06). Conclusion: This intervention of selected F& V did not lower β-glucuronidase activity. Further investigation is needed regarding what other foods and phytochemicals may influence β-glucuronidase activity and effect modifiers of this relation. (Cancer Epidemiol Biomarkers Prev 2008 (7):1808–12)
Publisher: Informa UK Limited
Date: 11-2011
Publisher: Elsevier BV
Date: 03-1997
DOI: 10.1016/S0304-3835(97)04615-6
Abstract: Perhaps the most promising lead to the prevention of cancer is derived from the epidemiologic observations that vegetables and fruit are consistently associated with lower risk of cancers of most epithelia. Over 200 studies have been undertaken, and a high proportion of them show lower risk with greater consumption. There are many plausible pathways to explain this risk reduction. The initial human experiments with specific single agents have proved to be disappointing. Single agents are not an advocated approach to chemotherapy, and may be inappropriate for chemoprevention. Foods may provide the optimal mix of phytochemicals and the best polypharmacy against the emergence of malignant clones.
Publisher: Springer Science and Business Media LLC
Date: 18-10-2007
DOI: 10.1007/S10552-007-9072-Y
Abstract: Vitamin E and selenium are promising nutrients for the prevention of prostate cancer, and both are currently being tested in a large randomized trial for prostate cancer. However, results are not expected for at least 6 years. We aimed to investigate the association of vitamin E and selenium supplementation with prostate cancer in the VITamins And Lifestyle (VITAL) study, a cohort study specifically designed to examine supplement use and future cancer risk. In a prospective design, 35,242 men recruited between 2000 and 2002 from western Washington State completed a questionnaire, including detailed questions about vitamin E and selenium supplement intake during the past 10 years from brand-specific multivitamins and single supplements. Using linkage to the western Washington SEER cancer registry, we documented 830 new cases of prostate cancer from baseline through December 2004. A 10-year average intake of supplemental vitamin E was not associated with a reduced prostate cancer risk overall [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.65-1.1 for > or =400 IU/day vs. non-use, p for trend 0.36] however, risk for advanced prostate cancer (regionally invasive or distant metastatic, n = 123) decreased significantly with greater intake of supplemental vitamin E (HR 0.43, 95% CI 0.19-1.0 for 10-year average intake > or =400 IU/day vs. non-use, p for trend 0.03). There was no association between selenium supplementation and prostate cancer risk (HR 0.90, 95% CI 0.62-1.3 for 10-year average intake >50 microg/day vs. non-use, p for trend 0.97). In this prospective cohort, long-term supplemental intake of vitamin E and selenium were not associated with prostate cancer risk overall however, risk of clinically relevant advanced disease was reduced with greater long-term vitamin E supplementation.
Publisher: Elsevier BV
Date: 05-2003
Publisher: Elsevier BV
Date: 06-2015
Publisher: American Association for Cancer Research (AACR)
Date: 11-2007
DOI: 10.1158/1055-9965.EPI-07-0120
Abstract: Background: Epidemiologic studies provide evidence that exercise is associated with reduced risk of colon cancer. Exercise may exert protective effects on the colon by influencing prostaglandin production. We hypothesized that an exercise intervention would decrease prostaglandin E2 concentrations and increase prostaglandin F2α in colon biopsies compared with controls. Methods: A 12-month randomized controlled trial testing the effects of exercise on colon mucosal prostaglandin concentrations was conducted in men (n = 95) and women (n = 89). The exercise intervention included moderate-to-vigorous aerobic activity, 60 min/d, 6 days/wk versus controls. Prostaglandin E2 and F2α concentrations were measured in colon biopsies using an enzyme-linked immunoassay at baseline and at 12 months to assess changes in mean concentration for each group. Results: Baseline colon prostaglandin E2 and F2α concentrations were not correlated with age, race, education, family history of colon cancer, previous polyps, body size, diet, smoking, nonsteroidal antiinflammatory drug use, metabolic factors, or sex hormone levels. For both men and women, the exercise and control groups showed no change in mean prostaglandin E2 or F2α between the baseline and 12-month biopsies. There was no difference in mean prostaglandin concentrations between exercisers and controls when exercisers were grouped by level of intervention adherence. Results were not modified by baseline age, body mass index, percentage of body fat, nonsteroidal antiinflammatory drug use, history of adenomatous polyps, or family history of colon cancer. Conclusion: A 12-month moderate-to-vigorous intensity aerobic exercise intervention did not result in significant changes in colon mucosal prostaglandin concentrations. (Cancer Epidemiol Biomarkers Prev 2007 (11):2351–6)
Publisher: Wiley
Date: 06-2007
DOI: 10.1038/OBY.2007.178
Abstract: The effect of national exercise recommendations on adiposity is unknown and may differ by sex. We examined long-term effects of aerobic exercise on adiposity in women and men. This was a 12-month randomized, controlled clinical trial testing exercise effect on weight and body composition in men (N = 102) and women (N = 100). Sedentary/unfit persons, 40 to 75 years old, were recruited through physician practices and media. The intervention was facility- and home-based moderate-to-vigorous intensity aerobic activity, 60 min/d, 6 days/wk vs. controls (no intervention). Exercisers exercised a mean 370 min/wk (men) and 295 min/wk (women), and seven dropped the intervention. Exercisers lost weight (women, -1.4 vs. +0.7 kg in controls, p = 0.008 men, -1.8 vs. -0.1 kg in controls, p = 0.03), BMI (women, -0.6 vs. +0.3 kg/m(2) in controls, p = 0.006 men, -0.5 kg/m(2) vs. no change in controls, p = 0.03), waist circumference (women, -1.4 vs. +2.2 cm in controls, p < 0.001 men, -3.3 vs. -0.4 cm in controls, p = 0.003), and total fat mass (women, -1.9 vs. +0.2 kg in controls, p = 0.001 men, -3.0 vs. +0.2 kg in controls, p < 0.001). Exercisers with greater increases in pedometer-measured steps per day had greater decreases in weight, BMI, body fat, and intra-abdominal fat (all p trend < 0.05 in both men and women). Similar trends were observed for increased minutes per day of exercise and for increases in maximal oxygen consumption. These data support the U.S. Department of Agriculture and Institute of Medicine guidelines of 60 min/d of moderate-to-vigorous physical activity.
Publisher: American Association for Cancer Research (AACR)
Date: 05-2013
DOI: 10.1158/1055-9965.EPI-12-1211
Abstract: Background: Previous reports suggest that relatives of colorectal cancer (CRC)-affected probands carrying the BRAF p.V600E mutation are at an increased risk of CRC and extracolonic cancers (ECC). In this study, we estimated the association between a family history of either CRC or ECC and risk of CRC with a BRAF p.V600E mutation. Methods: Population-based CRC cases (probands, ages 18–59 years at diagnosis), recruited irrespective of family cancer history, were characterized for BRAF p.V600E mutation and mismatch repair (MMR) status. ORs and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results: The 690 eligible probands showed a mean age at CRC diagnosis of 46.9 ± 7.8 years, with 313 (47.9%) reporting a family history of CRC and 53 (7.7%) that were BRAF-mutated. Probands with BRAF-mutated, MMR-proficient CRCs were less likely to have a family history of CRC than probands that were BRAF wild-type (OR, 0.46 95% CI, 0.24–0.91 P = 0.03). For probands with a BRAF-mutated CRC, the mean age at diagnosis was greater for those with a CRC-affected first- or second-degree relative (49.3 ± 6.4 years) compared with those without a family history (43.8 ± 10.2 years P = 0.04). The older the age at diagnosis of CRC with the BRAF p.V600E mutation, the more likely these probands were to show a family history of CRC (OR, 1.09 per year of age 95% CI, 1.00–1.18 P = 0.04). Conclusions: Probands with early-onset, BRAF-mutated, and MMR-proficient CRC were less likely to have a family history of CRC than probands that were BRAF-wild-type. Impact: These findings provide useful insights for cancer risk assessment in families and suggest that familial or inherited factors are more important in early-onset, BRAF-wild-type CRC. Cancer Epidemiol Biomarkers Prev 22(5) 917–26. ©2013 AACR.
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: To examine the incidence of colorectal cancer among Asian residents of the United States according to country of birth. We determined the incidence of colorectal cancer during 1973-1986 among Asian residents in three areas of the western United States (Hawaii, San Francisco/Oakland SMSA, and western Washington state) in relation to country of birth. Numerators for the rates were obtained from the Surveillance, Epidemiology and End Results (SEER) program a special tabulation of the 1980 US Census was used to estimate the size and composition of the population at risk. US-born Japanese men experienced incidence rates of colorectal cancer twice as high as foreign-born Japanese men and about 60% higher than those of US-born white men. Incidence among US-born Japanese women was about 40% higher than that among Japanese women born in Japan or US-born white women. Foreign-born Chinese men had about the same incidence of colorectal cancer as US-born white men, while US-born Chinese men experienced slightly reduced rates. Chinese women had rates that were generally 30-40% lower than that of US-born white women, regardless of place of birth. Incidence rates for both US-born and foreign-born Filipinos were 20-50% those of US-born whites. These findings suggest that one or more exposures or characteristics that differ between Japanese migrants and their descendants affect the development of colorectal cancer.
Publisher: Springer Science and Business Media LLC
Date: 07-07-2015
DOI: 10.1038/NCOMMS8138
Publisher: Springer Science and Business Media LLC
Date: 27-02-2006
Publisher: Wiley
Date: 27-09-2013
DOI: 10.1111/CGE.12011
Publisher: Elsevier BV
Date: 06-2010
Publisher: Springer Netherlands
Date: 2010
Publisher: Springer Science and Business Media LLC
Date: 11-1994
DOI: 10.1007/BF01831384
Publisher: American Association for Cancer Research (AACR)
Date: 12-2005
Publisher: American Association for Cancer Research (AACR)
Date: 06-2005
DOI: 10.1158/1055-9965.EPI-04-0694
Abstract: Insulin-like growth factors (IGFs) play key roles in cell proliferation and apoptosis. Whereas relatively stable within in iduals, IGFs vary substantially between in iduals, and a large component of this variation may be determined by genetic factors. Several polymorphisms in IGF genes have been identified, although their functional significance is not clear. We evaluated the association of polymorphisms in IGF-1 and IGFBP-3 and circulating levels of IGF-1 and IGFBP-3 in 323 population-based control subjects enrolled in a case-control study of colorectal cancer from September 1999 through February 2002. Total IGF-1 and IGFBP-3 levels were measured using ELISA assays, and all subjects were genotyped for a microsatellite polymorphism in IGF-1 and a single nucleotide polymorphism in IGFBP-3. Multiple linear regression was used to assess the association of genotype with circulating IGFs. IGF-1 levels were unrelated to either polymorphism. IGFBP-3 was significantly associated with IGFBP-3 genotype, with IGFBP-3 levels increasing from CC (1,895 ng/mL) → GC (2,029 ng/mL) → GG (2,182 ng/mL), (p-trend & 0.001). Having an IGF-1 genotype other than homozygous for the 19-repeat allele was associated with higher IGFBP-3 levels (1,945 versus 2,052 ng/mL). Furthermore, both IGF-1 and IGFBP-3 genotypes modified the relationship between postmenopausal hormone use and IGFs. This analysis provides evidence that common variation in IGF genes may contribute to the variation in circulating levels observed between in iduals.
Publisher: Springer Science and Business Media LLC
Date: 1997
Abstract: In this study, we evaluate diet ersity, diet composition, and risk of colon cancer in an incident population-based study of 1,993 cases and 2,410 controls in the Kaiser Permanente Medical Care Program of Northern California, eight counties in Utah, and the Twin Cities area of Minnesota (United States). Ninety-one and one-half percent of the population were non-Hispanic White. Dietary intake was obtained using an adaptation of the CARDIA diet-history questionnaire. Diet ersity was defined as the number of unique food items reported ersity also was explored within six major food groups. Composition of the diet was described by estimating the proportion of total number of food items contributed by major food groups. Younger in iduals, higher educated in iduals, and those who lived in larger households reported eating the most erse diet. Total diet ersity was not associated with colon cancer. However, eating a diet with greater ersity of meats, poultry, fish, and eggs, was associated with a 50 percent increase in risk among all men (95 percent confidence interval [CI] = 1.1-2.0 P trend = 0.01), with slightly stronger associations for younger men and men with distal tumors. A diet with a greater number of refined grain products also was associated with increased risk among men (odds ratio [OR] = 1.7, CI = 1.3-2.3). Women who ate a diet with a more erse pattern of vegetables were at approximately a 20 percent lower risk than women who had the least erse diet in vegetables. Assessment of diet composition showed that men who consumed a large proportion of their food items from meat, fish, poultry, and eggs were at an increased risk, with the most marked association being for distal tumors (OR = 1.7, CI = 1.2-2.5). Women who consumed the largest percentage of their food items in the form of plant foods (fruits, vegetables, or whole grains) were at a reduced risk of developing colon cancer (OR = 0.7, CI = 0.5-1.0).
Publisher: American Association for Cancer Research (AACR)
Date: 05-2005
DOI: 10.1158/1055-9965.EPI-04-0695
Abstract: Several modifiable lifestyle factors, such as physical activity, obesity, and postmenopausal hormone use, have been associated with colorectal cancer risk. It has been hypothesized that some or all of these factors may mediate their effects through alterations in insulin-like growth factor-1 (IGF-1) and its binding proteins (IGFBP). To evaluate the role of IGFs in colorectal cancer, we examined the relationship of two common genetic polymorphisms in IGF-1 (a cytosine-adenosine dinucleotide repeat) and IGFBP-3 (a G → C single nucleotide polymorphism) with colorectal cancer risk, as well as their potential modification by physical activity, body mass index (BMI), and postmenopausal hormone use. Subjects included 782 male and female colorectal cancer cases diagnosed between 1998 and 2002 and reported to the statewide registry in the metropolitan Seattle area, and 503 age- and sex-matched cancer-free population controls. Colorectal cancer was modestly associated with having an IGF-1 genotype other than homozygous for 19 repeats (odds ratio, 1.3 95% confidence interval, 1.0-1.6) and having the GG IGFBP-3 genotype (odds ratio, 1.3 95% confidence interval, 1.0-1.8). There was evidence that IGF-1 genotype modified the relationship between BMI and colorectal cancer among women, such that high BMI increased risk of colorectal cancer only among those with the 19/19 genotype (Pinteraction = 0.02). IGFBP-3 genotype was also a significant effect modifier of the relationship between risk factors and colorectal cancer: The positive association between BMI and colorectal cancer was observed only among men (Pinteraction & 0.01) and women (Pinteraction = 0.06) with the GG genotype the inverse association between postmenopausal hormone use and colorectal cancer was observed only among women with the GG genotype (P = 0.01) and the inverse association between physical activity and colorectal cancer was observed only among men who carried the C allele (P & 0.01). The current study provides some support for a role of IGFs in colorectal cancer etiology, particularly in mediating the relationship of common risk factors (physical activity, BMI, and postmenopausal hormone use).
Publisher: American Medical Association (AMA)
Date: 27-01-1993
Publisher: American Association for Cancer Research (AACR)
Date: 07-2006
DOI: 10.1158/0008-5472.CAN-06-1535
Abstract: Smoking has been consistently associated with an increased risk of colorectal adenomas and hyperplastic polyps as well as colorectal cancer. Conversely, nonsteroidal anti-inflammatory drugs (NSAID) have been associated with reduced colorectal cancer risk. We conducted a population-based case-control study to evaluate the joint association between smoking and regular NSAID use with colorectal cancer risk we also examined these associations stratified by tumor microsatellite instability (MSI). We analyzed 1,792 incident colorectal cancer cases and 1,501 population controls in the Seattle, Washington area from 1998-2002. MSI, defined as MSI high (MSI-H) or MSI-low/microsatellite stable (MSI-L/MSS), was assessed in tumors of 1,202 cases. Compared with nonsmokers, colorectal cancer risk was modestly increased among in iduals who had ever smoked. Current NSAID use was associated with a 30% lower risk compared with nonusers. There was a statistically significant interaction between smoking duration and use of NSAIDs (Pinteraction = 0.05): relative to current NSAID users who never smoked, in iduals who had both smoked for & years and had never used NSAIDs were at the highest risk for colorectal cancer (adjusted odds ratio, 2.8 95% confidence intervals, 1.8-4.1). Compared with nonsmokers, there was a stronger association within MSI-H tumors with current smoking than there was within MSI-L/MSS tumors. Smokers of long duration were at elevated risk of MSI-H tumors even with NSAID use. The risk of MSI-L/MSS tumors was not elevated among long-duration smokers with long exposure to NSAIDs but was elevated among long-duration smokers who had never used NSAIDs. There seems to be a synergistic inverse association (implying protection) against colorectal cancer overall as a result of NSAID use and nonsmoking, but risk of MSI-H colorectal cancer remains elevated among smokers even when they have a history of NSAID use. (Cancer Res 2006 66(13): 6877-83)
Publisher: Wiley
Date: 27-01-2010
DOI: 10.1002/IJC.25037
Publisher: American Medical Association (AMA)
Date: 05-1996
Publisher: Oxford University Press (OUP)
Date: 04-11-1992
Publisher: Elsevier BV
Date: 2009
Publisher: Oxford University Press (OUP)
Date: 18-11-2010
Publisher: American Association for Cancer Research (AACR)
Date: 10-2006
Publisher: Oxford University Press (OUP)
Date: 20-01-1993
Abstract: Colonic epithelial cell proliferation is increased in patients at high risk for colon cancer. Calcium administration has ameliorated the proliferative changes in rodents, and findings in small, uncontrolled clinical trials have suggested similar effects in humans. This preliminary, double-blind, randomized clinical trial was designed 1) to investigate whether supplemental calcium will reduce colonic epithelial cell proliferation in patients with sporadic adenomas who consume a high-fat, Western-style diet 2) to determine the s le size (number of scorable crypts per person) needed to achieve adequate statistical power and 3) to evaluate the feasibility of full-scale clinical trials. Twenty-one sporadic adenoma patients were treated daily with placebo or 1200 mg of supplemental calcium. To determine colonic epithelial cell proliferation, we used tritiated thymidine labeling of colon crypt epithelial cells in rectal biopsy specimens and calculated the percentage of labeled cells (labeling index [LI]). Two pathology technician "readers" independently scored each specimen, and inter-reader reliability was determined. Subjects remained on their usual diet during the study, and intake of calories, calcium, total fat, and vitamin D did not differ substantially among them. We calculated curves for statistical power to determine the number of scorable crypts needed per person for detection of a statistically significant difference (P < .05) of 1.0% in mean LI. The pooled baseline LI was 4.7%. In the calcium-treated group, the LI increased 0.6% (proportional increase, 12.8%) in the placebo-treated group, it decreased 0.5% (proportional decrease, 10.6%). The difference between change in the mean LI from baseline to 8 weeks' follow-up in the placebo group versus the calcium group was not statistically significant. The intraclass correlation coefficient for inter-reader reliability for the baseline LI was .66. Analyses indicated scoring eight crypts sufficient for estimates of the LI adequate for between-group comparisons, a level achieved in 81% of biopsy specimens. Calcium carbonate supplements delivering 1200 mg elemental calcium daily may not decrease colonic epithelial cell proliferation over an 8-week period in sporadic adenoma patients. In future trials measuring the LI, consideration should be given to ensuring adequate numbers of scorable crypts and to the impact of inadequate biopsy procedures, labeling failure, reader reliability, and participant withdrawal. Our findings support the feasibility of a full-scale clinical trial to further study the relationships among dietary calcium, colonic epithelial cell proliferation, and colorectal cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2015
DOI: 10.1158/1055-9965.EPI-15-0094
Abstract: Background: Microsatellite instability (MSI) and BRAF mutation status are associated with colorectal cancer survival, whereas the role of body mass index (BMI) is less clear. We evaluated the association between BMI and colorectal cancer survival, overall and by strata of MSI, BRAF mutation, sex, and other factors. Methods: This study included 5,615 men and women diagnosed with invasive colorectal cancer who were followed for mortality (maximum: 14.7 years mean: 5.9 years). Prediagnosis BMI was derived from self-reported weight approximately one year before diagnosis and height. Tumor MSI and BRAF mutation status were available for 4,131 and 4,414 persons, respectively. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated from delayed-entry Cox proportional hazards models. Results: In multivariable models, high prediagnosis BMI was associated with higher risk of all-cause mortality in both sexes (per 5-kg/m2 HR, 1.10 95% CI, 1.06–1.15), with similar associations stratified by sex (Pinteraction: 0.41), colon versus rectum (Pinteraction: 0.86), MSI status (Pinteraction: 0.84), and BRAF mutation status (Pinteraction: 0.28). In joint models, with MS-stable/MSI-low and normal BMI as the reference group, risk of death was higher for MS-stable/MSI-low and obese BMI (HR, 1.32 P value: 0.0002), not statistically significantly lower for MSI-high and normal BMI (HR, 0.86 P value: 0.29), and approximately the same for MSI-high and obese BMI (HR, 1.00 P value: 0.98). Conclusions: High prediagnosis BMI was associated with increased mortality this association was consistent across participant subgroups, including strata of tumor molecular phenotype. Impact: High BMI may attenuate the survival benefit otherwise observed with MSI-high tumors. Cancer Epidemiol Biomarkers Prev 24(8) 1229–38. ©2015 AACR.
Publisher: Oxford University Press (OUP)
Date: 05-05-2022
DOI: 10.1093/JNCI/DJAC094
Abstract: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2– or 3–degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78 OR = 0.65, 95% CI = 0.53 to 0.79 and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2–degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P & 1.2 × 10−4). Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
Publisher: Wiley
Date: 15-03-1999
DOI: 10.1002/(SICI)1097-0142(19990315)85:6<1380::AID-CNCR23>3.0.CO;2-O
Publisher: American Association for Cancer Research (AACR)
Date: 12-2014
DOI: 10.1158/1055-9965.EPI-14-0893
Abstract: Background: Calcium intake may reduce risk of colorectal cancer, but the mechanisms remain unclear. Studies of interaction between calcium intake and SNPs in calcium-related pathways have yielded inconsistent results. Methods: To identify gene–calcium interactions, we tested interactions between approximately 2.7 million SNPs across the genome with self-reported calcium intake (from dietary or supplemental sources) in 9,006 colorectal cancer cases and 9,503 controls of European ancestry. To test for multiplicative interactions, we used multivariable logistic regression and defined statistical significance using the conventional genome-wide α = 5E−08. Results: After accounting for multiple comparisons, there were no statistically significant SNP interactions with total, dietary, or supplemental calcium intake. Conclusions: We found no evidence of SNP interactions with calcium intake for colorectal cancer risk in a large population of 18,509 in iduals. Impact: These results suggest that in genome-wide analysis common genetic variants do not strongly modify the association between calcium intake and colorectal cancer in European populations. Cancer Epidemiol Biomarkers Prev 23(12) 2971–6. ©2014 AACR.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 20-12-2022
Publisher: American Association for Cancer Research (AACR)
Date: 04-2008
DOI: 10.1158/1055-9965.EPI-07-2687
Abstract: Polymorphisms of the transcription factor 7–like 2 (TCF7L2) gene have been associated with insulin sensitivity and diabetes, and the TCF7L2 gene is involved in the Wnt/β-catenin signaling pathway, all factors thought to be important in the etiology of colon cancer. In this confirmatory study, we evaluated the rs7903146 TCF7L2 polymorphism with colon cancer using previously collected data on 1,578 cases and 1,966 controls. We did not observe a statistically significant association between the rs7903146 polymorphisms and risk of colon cancer [odds ratio (OR), 1.12 95% confidence interval (95% CI), 0.98-1.28] when evaluating the total population. We did, however, observe a statistically significant interaction between the rs7903146 TCF7L2 polymorphism and recent use of aspirin/nonsteroidal anti-inflammatory drugs (NSAID P = 0.001). Increased colon cancer risk associated with the T allele was restricted to those without recent use of aspirin/NSAIDs (OR, 1.65 95% CI, 1.35-2.02, relative to recent aspirin users, i.e., use of aspirin/NSAIDS within the 2 years before diagnosis, with the CC genotype). Among in iduals who reported recent use of aspirin/NSAIDs, the T allele reduced risk of colon cancer (OR, 0.78 95% CI, 0.62-0.98) in a dose-response fashion (P for linear trend across genotypes = 0.03). These data suggest that colon cancer risk associated with the rs7903146 TCF7L2 polymorphism is modified by use of aspirin/NSAIDs. (Cancer Epidemiol Biomarkers Prev 2008 (4):978–82)
Publisher: Mary Ann Liebert Inc
Date: 04-2008
Abstract: Pathway analysis of microarray data evaluates gene expression profiles of a priori defined biological pathways in association with a phenotype of interest. We propose a unified pathway-analysis method that can be used for erse phenotypes including binary, multiclass, continuous, count, rate, and censored survival phenotypes. The proposed method also allows covariate adjustments and correlation in the phenotype variable that is encountered in longitudinal, cluster-s led, and paired designs. These are accomplished by combining the regression-based test statistic for each in idual gene in a pathway of interest into a pathway-level test statistic. Applications of the proposed method are illustrated with two real pathway-analysis ex les: one evaluating relapse-associated gene expression involving a matched-pair binary phenotype in children with acute lymphoblastic leukemia and the other investigating gene expression in breast cancer tissues in relation to patients' survival (a censored survival phenotype). Implementations for various phenotypes are available in R. Additionally, an Excel Add-in for a user-friendly interface is currently being developed.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2015
Publisher: Springer Science and Business Media LLC
Date: 1997
Abstract: This report reviews published epidemiologic research on the associations of vitamin and mineral supplementation with cancer risk. Although the literature on nutrition and cancer is vast, few reports to date have addressed supplemental nutrients directly (seven clinical trials, 16 cohort, and 36 case-control studies). These studies offer insight into effects of nutrients that are distinguishable from effects of other biologically active compounds in foods. Randomized clinical trials have not shown significant protective effects of beta-carotene, but have found protective effects of: alpha-tocopherol against prostate cancer mixtures of retinol/zinc and beta-carotene/alpha-tocopherol/selenium against stomach cancer and selenium against total, lung, and prostate cancers. Cohort studies provide little evidence that vitamin supplements are associated with cancer. Case-control studies have reported an inverse association between bladder cancer and vitamin C oral haryngeal cancer and several supplemental vitamins and several cancers and vitamin E. A randomized clinical trial, a cohort study, and a case-control study have all found inverse associations between colon cancer and vitamin E. Overall, there is modest evidence for protective effects of nutrients from supplements against several cancers. Future studies of supplement use and cancer appear warranted however, methodologic problems that impair ability to assess supplement use and statistical modeling of the relation between cancer risk and supplement use need attention.
Publisher: Oxford University Press (OUP)
Date: 15-11-2003
DOI: 10.1093/AJE/KWG248
Abstract: The higher incidence of colon cancer in African Americans compared with other US racial/ethnic groups is largely unexplained. This report describes associations of total energy and macronutrients with colon cancer risk in African Americans and Whites from a case-control study in North Carolina between 1996 and 2000. Incident cases of histologically confirmed colon cancer, aged 40-80 years (n = 613), and matched controls (n = 996) were interviewed in person to elicit information on potential colon cancer risk factors. A validated food frequency questionnaire adapted to include regional foods was used to assess diet over the year prior to diagnosis or interview date. Cases generally reported higher mean daily intakes of total energy and macronutrients and lower dietary fiber consumption than did controls. Total energy intake was positively associated with colon cancer risk in both racial groups and, although there were some differences by race, high intakes of in idual energy sources were also generally associated with two- to threefold increases in risk in models not controlled for total energy. However, these associations largely disappeared when total energy was taken into account. A high level of dietary fiber was associated with a statistically significant 50-60% risk reduction in African Americans and a nonsignificant 30% decreased risk in Whites. Alcohol intake was not statistically significantly associated with colon cancer in either racial group. Total energy intake was consistently associated with colon cancer risk, but associations with in idual macronutrients varied somewhat by race and by adjustment for energy intake. These findings may provide an explanation for some of the racial differences in colon cancer incidence.
Publisher: Oxford University Press (OUP)
Date: 1990
DOI: 10.1093/HER/5.4.421
Publisher: American Association for Cancer Research (AACR)
Date: 05-2005
DOI: 10.1158/1055-9965.EPI-04-0681
Abstract: The peroxisome proliferator–activated receptor γ (PPARγ) is one of a group of ligand-activated nuclear receptors responsible for regulation of glucose, lipid homeostasis, cell differentiation, and apoptosis. The 12 proline-to-alanine (Pro12Ala) substitution polymorphism in PPARγ produces proteins with lower activity. Variation in PPARγ expression in the bowel and the role of dietary fatty acids as ligands for PPARγ led investigation of whether the associations of diet with colon and rectal cancer risk were modified by PPARγ genotype. Data (diet, lifestyle, and DNA) came from case-control studies of colon (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls) conducted in Northern California, Utah, and the Twin City, Minnesota Metropolitan area (colon cancer study only). Unconditional logistic regression models were adjusted for age at selection, body mass index, physical activity, energy intake, dietary fiber, and calcium. We found no significant interactions between macronutrient (fat, protein, and carbohydrate) and colorectal cancer. High lutein intake [odds ratio (OR), 0.63 95% confidence interval (95% CI), 0.44-0.89], low refined grain intake (OR, 0.70 95% CI, 0.53-0.94), or a high prudent diet score (OR, 0.66 95% CI, 0.49-0.89) and PA/AA PPARγ genotype were associated with reduced colon cancer risk. Risk of rectal cancer was increased among those with the PA/AA PPARγ genotype and a high mutagen index (OR, 1.63 95% CI, 1.12, 2.36). Its unclear whether the alterations in risk in those with the less active phenotype for PPARγ is related to activation of PPARγ by nutrients or dietary patterns acting as ligands or direct influences of these nutrients on colon and rectal cancer processes that are important with lower PPARγ activity.
Publisher: Oxford University Press (OUP)
Date: 15-03-2003
DOI: 10.1093/AJE/KWG007
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: Family history of cancer has been a useful tool to identify highly penetrant genes. However, the association between family history and low-penetrance genes that are prevalent in the population, is less well understood. While epidemiologists have studied low-penetrance genes in association studies at the population level, geneticists have often favored family studies to identify low-penetrance genes in the same manner that these families have been used to identify high-penetrance genes. In this study, we evaluated the association between family history of cancer and molecular variants of three genes: N-acetyltransferases (NAT2), glutathione-S-transferases (GSTM-1), and methylenetetrahydrofolate reductase (MTHFR). These genes were examined because of their plausible functional significance and their association with cancer risk in some studies. In a large multi-centered study of colon cancer, reported family history of cancer in first-degree relatives was used to classify cases and controls separately as having a family history of colorectal cancer, hormone-related cancers, smoking-related cancers, prostate cancer, and any cancer. With three weak exceptions, we did not observe significant associations between any of these genes and family history of cancer. The ability of family history to positively predict the presence of variants of low-penetrance genes that may carry an elevated risk ranged from 41% to 60% low-penetrance variants accurately predicted a family history of cancer 9 to 17% of the time. Assessment of the likelihood of having a family history of cancer given the combination of genetic and environmental factors, showed that those who smoked 20 or more cigarettes per day were more likely to have a family history of a smoking-related cancer irrespective of genotype. People with a family history of cancer are not more likely to have a variant of low-penetrance genes than those without a family history of cancer. Family studies may not be efficient methods to study low-penetrance genes.
Publisher: American Association for Cancer Research (AACR)
Date: 2015
DOI: 10.1158/1055-9965.EPI-14-0897
Abstract: Background: Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and colorectal cancer has been inconsistently reported. Methods: We used pooled in idual-level data from the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results: From 11 studies, 8,290 colorectal cancer cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of colorectal cancer compared with the lowest quartile [OR, 1.41 95% confidence interval (CI), 1.29–1.55]. However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with colorectal cancer in those with a rapid/intermediate NAT2 genotype (OR, 1.38 95% CI, 1.20–1.59) as with a slow genotype (OR, 1.43 95% CI, 1.28–1.61 P interaction = 0.9). Conclusion: We found that high red meat intake was associated with increased risk of colorectal cancer only from retrospective case–control studies and not modified by NAT2 enzyme activity. Impact: Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 24(1) 198–205. ©2014 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 31-07-2014
DOI: 10.1158/1055-9965.EPI-14-0533
Abstract: Background: In iduals with a family history of colorectal cancer in first-degree relatives have an elevated risk of developing colorectal cancer themselves, particularly colorectal cancer exhibiting high microsatellite instability (MSI-high). Given that MSI-high colorectal cancer is associated with a favorable prognosis, it is plausible that having a family history of colorectal cancer could, in turn, be favorably associated with colorectal cancer survival. Methods: This study comprised N = 4,284 incident colorectal cancer cases enrolled in the Colon Cancer Family Registry via population-based cancer registries. Using Cox proportional hazards regression, we evaluated the association between family history and both overall and disease-specific survival, accounting for MSI status and tumor site via stratified analyses and statistical adjustment. Results: There was no evidence of association between family history and overall [hazard ratio (HR), 0.92 95% confidence interval (CI), 0.79–1.08] or disease-specific survival (HR, 1.03 95% CI, 0.85–1.24) for all cases combined, after adjustment for MSI status or tumor site. Only for rectal cancer cases was colorectal cancer family history modestly associated with more favorable overall survival (HR, 0.75 95% CI, 0.56–0.99). Conclusions: Although in iduals with a family history of colorectal cancer were more likely to have MSI-high tumors than those with nonfamilial disease, this did not translate to a survival benefit. Impact: Overall, there is no evidence that family history of colorectal cancer is associated with colorectal cancer survival however, specific mechanisms underlying family history may have prognostic impact and merit further study. Cancer Epidemiol Biomarkers Prev 23(8) 1700–4. ©2014 AACR.
Publisher: Massachusetts Medical Society
Date: 24-02-2011
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 20-04-2005
Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs), used for the treatment of pain and inflammation, are eliminated primarily through conjugation with polar sugar moieties to form glucuronides. Glucuronidation is catalyzed by the UDP-glucuronosyltransferases (UGT) superfamily. An inverse relationship may exist between glucuronidation activity and NSAID efficacy however, specific UGTs catalyzing conjugation of the structurally erse NSAIDs have yet to be identified systematically. Therefore, NSAID glucuronidation activity by 12 in idually expressed UGTs was investigated by liquid chromatography-tandem mass spectrometry. The relative rates of NSAID glucuronidation varied among UGT enzymes examined, demonstrating specificity of the in idual UGTs toward selected NSAIDs. Kinetic parameters were determined for expressed UGT Supersomes and compared with parameters determined in pooled human liver microsomes (HLMs). Comparison of K(m) values suggested roles for UGTs 1A3 and 2B7 in indene glucuronidation and UGTs 1A9, 2B4, and 2B7 in profen glucuronidation. Inhibitory studies in pooled HLMs support the role of UGTs 1A1, 1A3, 1A9, 2B4, and 2B7 in the glucuronidation of ibuprofen, flurbiprofen, and ketoprofen. Bilirubin did not inhibit indomethacin or diclofenac glucuronidation, suggesting that UGT1A1 was not involved in catalysis. Imipramine did not inhibit glucuronidation of sulindac, sulindac sulfone, indomethacin, or naproxen in pooled HLMs, suggesting that UGT1A3 was not a principal hepatic catalyst. Nevertheless, multiple UGT enzymes, most notably UGTs 1A1, 1A9, 2B4, and 2B7, seem to be involved in the hepatic catalysis of NSAID glucuronidation.
Publisher: Elsevier BV
Date: 09-2023
Publisher: American Association for Cancer Research (AACR)
Date: 30-04-2013
DOI: 10.1158/0008-5472.CAN-12-3462
Abstract: A subset of aggressive colorectal cancers exhibit BRAF mutation, MLH1 methylation, and a CpG island methylator phenotype (CIMP), but precursors are poorly established. In this study, we determined the status of these markers in colorectal polyps and evaluated associated risk factors. The study included 771 polyp cases and 1,027 controls who were ages 24 to 80 years, part of a group health program, received a colonoscopy from 1998 to 2007, and completed a structured questionnaire assessing risk factors. Following standard pathology review, polyps were assayed for BRAF mutation (V600E) and tested for MLH1 and CIMP methylation, the latter including the genes, CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1. Polytomous logistic regression was used to estimate ORs and 95% confidence intervals for the association between molecularly defined subsets of polyps and potential risk factors. There were 580 conventional adenomas and 419 serrated lesions successfully assayed. For adenomas, the prevalence of each marker was ≤1%. In contrast, 55% of serrated lesions harbored mutant BRAF, 26% were CIMP-high, and 5% had methylated MLH1. In these lesions, the highest prevalence of markers was in sessile-serrated polyps (SSP) of ≥10 mm that were in the right-side/cecal regions of the colon. Risk factors for CIMP-high–serrated lesions included Caucasian race, current smoking status, and a history of polyps, whereas for serrated lesions with mutant BRAF, the significant risk factors were male sex, current smoking status, obesity, and a history of polyps. Our results suggest that SSPs and other large, right-sided serrated lesions have a unique molecular profile that is similar to CIMP-high, BRAF-mutated colorectal cancers. Cancer Res 73(9) 2863–72. ©2013 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2009
DOI: 10.1158/1055-9965.EPI-09-0589
Abstract: Cytochrome P-450 1A2 (CYP1A2) is a biotransformation enzyme that activates several procarcinogens. CYP1A2 is induced by cruciferous and inhibited by apiaceous vegetable intake. Using a randomized, crossover feeding trial in humans, we investigated the dose effects of cruciferous vegetables and the effects of any interaction between cruciferous and apiaceous vegetables on CYP1A2 activity. We also investigated whether response varied by CYP1A2*1F, GSTM1, and GSTT1 genotypes (glutathione S-transferases that metabolize crucifer constituents) and whether CYP1A2 activity rebounds after apiaceous vegetables are removed from the diet. Participants (N = 73), recruited based on genotypes, consumed four diets for two weeks each: low-phytochemical diet (basal), basal plus single dose of cruciferous (1C), basal plus double dose of cruciferous (2C), and basal plus single dose of cruciferous and apiaceous vegetables (1C+A). CYP1A2 activity was determined by urine caffeine tests administered at baseline and the end of each feeding period. Compared with basal diet, the 1C diet increased CYP1A2 activity (P & 0.0001) and the 2C diet resulted in further increases (P & 0.0001), with men experiencing greater dose-response than women. The 1C+A diet decreased CYP1A2 activity compared with the 1C and 2C diets (P & 0.0001 for both). Although there was no overall effect of CYP1A2*1F or GSTM1-null/GSTT1-null genotypes or genotype-by-diet interactions, there were significant diet response differences within each genotype. Additionally, CYP1A2 activity recovered modestly one day after the removal of apiaceous vegetables. These results suggest complex interactions among dietary patterns, genetic variation, and modulation of biotransformation that may not be apparent in observational studies. (Cancer Epidemiol Biomarkers Prev 2009 (11):3118–25)
Publisher: American Association for Cancer Research (AACR)
Date: 09-2009
DOI: 10.1158/1055-9965.EPI-09-0228
Abstract: Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor (VDR), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-α hydroxylase (CYP27B1) and vitamin D deactivating enzyme 24-α hydroxylase (CYP24A1). We evaluated whether 12 tagging single nucleotide polymorphisms (SNP) in CYP24A1, identified by resequencing the gene in 32 Caucasian s les, and 1 SNP in CYP27B1 were associated with colon cancer risk. In addition, we evaluated whether these two genes modify associations between colon cancer on the one hand and total vitamin D intake and UV-weighted sun exposure on the other, as well as other variants in VDR. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between polymorphisms and haplotypes in CYP27B1 and CYP24A1 in a multicenter population-based case-control study of 1,600 cases and 1,949 controls. The CYP24A1 polymorphism IVS4-66T & G showed a statistically significant association with risk of colon cancer overall, particularly for proximal colon cancer. When stratified by anatomic site, we also found statistically significant associations for three CYP24A1 polymorphisms with risk of distal colon cancer (IVS4 + 1653C & T: OR for CT/TT versus CC, 0.81 95% CI, 0.68-0.96 IVS9 + 198T & C: OR for CC versus TT, 1.33 95% CI, 1.03-1.73 and within whites only: +4125bp 3′ of STPC & G: OR for GG versus CC, 1.44 95% CI, 1-2.05). In addition, a possible interaction between CYP27B1 and UV-weighted sun exposure with proximal colon cancer was observed. As this is the first study to evaluate these genes in relation to colon cancer, additional studies are needed to confirm these results. (Cancer Epidemiol Biomarkers Prev 2009 (9):2540–8)
Publisher: Springer Science and Business Media LLC
Date: 23-09-2002
DOI: 10.1038/NG989
Publisher: Wiley
Date: 18-11-2006
Publisher: Springer Science and Business Media LLC
Date: 25-01-2015
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22426015.V1
Abstract: Supplementary Table S7
Publisher: American Association for Cancer Research (AACR)
Date: 09-2007
DOI: 10.1158/1055-9965.EPI-07-0151
Abstract: Introduction: Colorectal adenomas and other types of polyps are commonly used as end points or risk factors in epidemiologic studies. However, it is not known how accurately patients are able to self-report the presence or absence of adenomas following colonoscopy. Methods: Participants in the Colon Cancer Family Registry provided self-reports of recent colorectal cancer (CRC) screening activity, and whether or not they had ever been told they had a polyp. Positive and negative predictive values for polyp self-report were calculated by comparing medical records with self-reports from 488 participants. Results: The positive predictive value for self-reported polyp was 80.9%, and the negative predictive value was 85.8%. The predictive values did not differ by age group or sex, but participants with a previous diagnosis of CRC had a lower negative predictive value (76.2%) than participants with no personal history of CRC (89.0% P = 0.04). Conclusions: Predictive values for self-reports of polyps are fairly high, but researchers needing accurate polyp data should obtain medical record confirmation. Pursuing medical records on only those participants self-reporting a polyp could result in an underestimation of the polyp prevalence in a study population. (Cancer Epidemiol Biomarkers Prev 2007 (9):1898–901)
Publisher: Elsevier BV
Date: 1979
DOI: 10.1016/S0140-6736(79)90634-2
Abstract: The stable globin mRNAs provide an ideal system for studying the mechanism governing mammalian mRNA turnover. alpha-Globin mRNA stability is dictated by sequences in the 3' untranslated region (3'UTR) which form a specific ribonucleoprotein complex (alpha-complex) whose presence correlates with mRNA stability. One of the major protein components within this complex is a family of two polycytidylate-binding proteins, alphaCP1 and alphaCP2. Using an in vitro-transcribed and polyadenylated alpha-globin 3'UTR, we have devised an in vitro mRNA decay assay which reproduces the alpha-complex-dependent mRNA stability observed in cells. Incubation of the RNA with erythroleukemia K562 cytosolic extract results in deadenylation with distinct intermediates containing a periodicity of approximately 30 nucleotides, which is consistent with the binding of poly(A)-binding protein (PABP) monomers. Disruption of the alpha-complex by sequestration of alphaCP1 and alphaCP2 enhances deadenylation and decay of the mRNA, while reconstitution of the alpha-complex stabilizes the mRNA. Similarly, PABP is also essential for the stability of mRNA in vitro, since rapid deadenylation resulted upon its depletion. An RNA-dependent interaction between alphaCP1 and alphaCP2 with PABP suggests that the alpha-complex can directly interact with PABP. Therefore, the alpha-complex is an mRNA stability complex in vitro which could function at least in part by interacting with PABP.
Publisher: American Association for Cancer Research (AACR)
Date: 14-11-2011
DOI: 10.1158/1078-0432.CCR-11-1134
Abstract: Purpose: Prognosis of patients with colorectal cancer (CRC) is associated with systemic inflammation, and anti-inflammatory drugs can reduce both CRC incidence and mortality. Genetic variation in proinflammatory pathways can affect an in idual's CRC risk. However, few studies have investigated the prognostic importance of this genetic variation in CRC patients. Experimental Design: We investigated the association between CRC survival and genetic variation in proinflammatory pathways among patients from the Puget Sound Surveillance Epidemiology and End Results registry. Single-nucleotide polymorphisms were genotyped in five genes (PTGS-1, PTGS-2, MRP4, NFκB, and IκBKβ). Vital status was ascertained through linkage to the National Death Index. Cox proportional hazards regression was used to calculate HRs and 95% confidence intervals (CI). The false discovery rate method of Benjamini and Hochberg was applied to address multiple testing. Results: Four PTGS-1 variants were associated with CRC survival. One, G& A intron 9 (rs1213266), was associated with approximately 50% lower CRC mortality (HRAA/AG vs. GG = 0.48 95% CI, 0.25–0.93). Three variants, including L237M, resulted in significantly elevated CRC mortality risk, with HRs ranging from approximately 1.5 to 2.0. Two variants in IκBKβ, including R526Q, were significantly associated with CRC survival. Correction for multiple testing indicated that variants in both PTGS-1 and IκBKβ are reproducibly associated with CRC survival. Conclusion: Our findings suggest that genetic variation in proinflammatory pathways may be important for CRC prognosis. This investigation represents one of the first descriptions of the relationship between inherited polymorphisms and mortality in CRC patients and provides a starting point for further research. Clin Cancer Res 17(22) 7139–47. ©2011 AACR.
Publisher: Elsevier BV
Date: 06-2010
Publisher: Wiley
Date: 12-03-2002
DOI: 10.1002/MPO.1316
Abstract: Increased attention has been directed toward the long-term health outcomes of survivors of childhood cancer. To facilitate such research, a multi-institutional consortium established the Childhood Cancer Survivor Study (CCSS), a large, erse, and well-characterized cohort of 5-year survivors of childhood and adolescent cancer. Eligibility for the CCSS cohort included a selected group of cancer diagnoses prior to age 21 years between 1970-1986 and survival for at least 5 years. A total of 20,276 eligible subjects were identified from the 25 contributing institutions, of whom 15% are considered lost to follow-up. Currently, 14,054 subjects (69.3% of the eligible cohort) have participated by completing a 24-page baseline questionnaire. The distribution of first diagnoses includes leukemia (33%), lymphoma (21%), neuroblastoma (7%), CNS tumor (13%), bone tumor (8%), kidney tumor (9%), and soft-tissue sarcoma (9%). Abstraction of medical records for chemotherapy, radiation therapy, and surgical procedures has been successfully completed for 98% of study participants. Overall, 78% received radiotherapy and 73% chemotherapy. The CCSS represents the largest and most extensively characterized cohort of childhood and adolescent cancer survivors in North America. It serves as a resource for addressing important issues such as risk of second malignancies, endocrine and reproductive outcome, cardiopulmonary complications, and psychosocial implications, among this unique and ever-growing population.
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: The hypothesis that antibiotic use may increase cancer risk was first proposed several decades ago and some research suggests an increased risk of breast cancer among women with conditions likely to require long-term antibiotic use (e.g., acne, recurrent urinary-tract infections, UTI). However, this hypothesis has not been verified and the possible biological mechanisms are not entirely clear. A recent cohort study in Finland reported an increased risk of breast-cancer associated with antibiotic use for UTI. The effect of antibiotics on the ability of intestinal microflora to metabolise phytochemicals from edible plants into compounds that may protect against cancer was proposed as a potential mechanism. We extend this hypothesis by proposing that antibiotic use may be associated with breast-cancer risk through effects on immune and inflammatory factors, such as cytokines, T lymphocytes, prostaglandins, and matrix metalloproteinases, as well as disruption of phytochemical and oestrogen metabolism by intestinal microflora. We suggest that some mechanisms may increase breast-cancer risk, while others may decrease risk, depending on the antibiotic classification.
Publisher: Oxford University Press (OUP)
Date: 15-11-2003
DOI: 10.1093/AJE/KWG236
Abstract: High insulin levels have been associated with increased risk of breast cancer and poorer survival after a breast cancer diagnosis. Waist-to-hip ratio (WHR) is a marker for insulin resistance and hyperinsulinemia. In this study, the authors tested the hypothesis that elevated WHR is directly related to breast cancer mortality. For identification of modifiable factors affecting survival, data were collected on 603 patients with incident breast cancer who visited the Vancouver Cancer Centre of the British Columbia Cancer Agency (Vancouver, British Columbia, Canada) in 1991-1992, including body measurements and information on demographic, medical, reproductive, and dietary factors. These patients were followed for up to 10 years. Cox proportional hazards regression models were used to relate the variables to breast cancer mortality (n = 112). After adjustment for age, body mass index, family history, estrogen receptor (ER) status, tumor stage at diagnosis, and systemic treatment (chemotherapy or tamoxifen), WHR was directly related to breast cancer mortality in postmenopausal women (for highest quartile vs. lowest, relative risk = 3.3, 95% confidence interval: 1.1, 10.4) but not in premenopausal women (relative risk = 1.2, 95% confidence interval: 0.4, 3.4). Stratification according to ER status showed that the increased mortality was restricted to ER-positive postmenopausal women. Elevated WHR was confirmed as a predictor of breast cancer mortality, with menopausal status and ER status at diagnosis found to be important modifiers of that relation.
Location: United States of America
Location: United States of America
Location: New Zealand
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Start Date: 2021
End Date: 2024
Funder: Marsden Fund
View Funded ActivityStart Date: 2013
End Date: 2016
Funder: Genesis Oncology Trust
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