ORCID Profile
0000-0002-5803-310X
Current Organisations
University of California, Berkeley
,
Kaiser Permanente
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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: 06-2018
Publisher: Springer Science and Business Media LLC
Date: 11-04-2011
Publisher: MDPI AG
Date: 28-09-2017
Publisher: Springer Science and Business Media LLC
Date: 28-02-2019
Publisher: BMJ
Date: 03-06-2008
Publisher: Oxford University Press (OUP)
Date: 21-02-2014
DOI: 10.1093/HMG/DDU087
Publisher: Elsevier BV
Date: 04-2013
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: Wiley
Date: 28-11-2010
DOI: 10.1002/IJC.25721
Publisher: Springer Science and Business Media LLC
Date: 15-07-2011
Publisher: Informa UK Limited
Date: 11-2011
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: Elsevier BV
Date: 10-2014
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: 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: 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: Springer Science and Business Media LLC
Date: 08-06-2012
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: 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: 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: Springer Science and Business Media LLC
Date: 07-07-2015
DOI: 10.1038/NCOMMS8138
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: 12-06-2015
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: Oxford University Press (OUP)
Date: 13-06-2015
DOI: 10.1093/JNCI/DJV160
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: 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: 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: 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: 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: Wiley
Date: 27-04-2011
DOI: 10.1002/IJC.26047
Publisher: Springer Science and Business Media LLC
Date: 12-2010
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: Wiley
Date: 25-01-2008
DOI: 10.1002/IJC.23135
Publisher: American Association for Cancer Research (AACR)
Date: 05-2005
Publisher: Springer Science and Business Media LLC
Date: 24-05-2018
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: Elsevier BV
Date: 2009
Publisher: Wiley
Date: 07-09-2012
Publisher: Oxford University Press (OUP)
Date: 18-11-2010
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: Springer Science and Business Media LLC
Date: 28-06-2019
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: Wiley
Date: 27-02-2012
DOI: 10.1002/GCC.21946
Publisher: Springer Science and Business Media LLC
Date: 03-12-2018
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: Wiley
Date: 06-07-2009
DOI: 10.1002/MC.20566
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: Elsevier BV
Date: 04-2012
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: 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: 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: Public Library of Science (PLoS)
Date: 26-12-2012
Publisher: Oxford University Press (OUP)
Date: 21-11-2018
DOI: 10.1093/IJE/DYY244
Abstract: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. In idual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10–4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04 95% confidence interval (CI): 0.97, 1.12 P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among in iduals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.
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: Wiley
Date: 09-07-2008
DOI: 10.1002/GCC.20584
Publisher: Public Library of Science (PLoS)
Date: 17-04-2014
Publisher: Springer Science and Business Media LLC
Date: 13-08-2007
Publisher: Wiley
Date: 07-06-2020
DOI: 10.1002/IJC.32377
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: Wiley
Date: 12-02-2013
DOI: 10.1002/GCC.22042
Publisher: Springer Science and Business Media LLC
Date: 11-09-2013
Publisher: Oxford University Press (OUP)
Date: 16-06-2018
DOI: 10.1093/JNCI/DJY099
Abstract: Previous genome-wide association studies (GWAS) have identified 42 loci (P 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic s le (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P 5 × 10−8) were tested for replication in separate European ancestry s les (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. The discovery GWAS identified 11 variants associated with CRC at P 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7% known variants) to 11.9% (95% CI = 9.2% to 15.5% known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for in idualized screening.
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: 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: 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: 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: BMJ
Date: 09-08-2013
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.
Location: United States of America
No related grants have been discovered for Bette Caan.