ORCID Profile
0000-0003-1761-6314
Current Organisations
Aichi Cancer Center Research Institute
,
Nagoya University
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Publisher: Springer Science and Business Media LLC
Date: 13-02-2023
Publisher: Springer Science and Business Media LLC
Date: 03-01-2017
Publisher: Wiley
Date: 24-01-2017
DOI: 10.1002/IJC.30600
Publisher: American Association for Cancer Research (AACR)
Date: 02-2019
DOI: 10.1158/0008-5472.CAN-18-2726
Abstract: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
Publisher: Elsevier BV
Date: 04-2013
Publisher: Springer Science and Business Media LLC
Date: 07-09-2016
DOI: 10.1038/SREP32512
Abstract: Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92 CI 0.90–0.94 P = 8.96 × 10 −15 )) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10 −09 , r 2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10 −11 , r 2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.
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: Springer Science and Business Media LLC
Date: 05-03-2020
DOI: 10.1038/S41467-020-15046-W
Abstract: Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P 5 × 10 −8 . The associations for 10 of these loci were replicated in an independent s le of 16,787 cases and 16,680 controls of Asian women ( P 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
Publisher: MDPI AG
Date: 13-04-2022
Abstract: Objective: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC. Methods: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated. Results: A total of 176 women with LGSC were included in this study 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99 95%CI, 0.96–1.01 and 0.98 95%CI 0.95–1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43–12.73) and OS (HR 1.69, 95%CI 0.56–5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36–5.81) and OS (HR 6.62, 95%CI 2.45–17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85). Conclusion: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS. Highlights: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.
Publisher: Oxford University Press (OUP)
Date: 11-07-2016
DOI: 10.1093/HMG/DDW223
Publisher: Springer Science and Business Media LLC
Date: 15-11-2016
DOI: 10.1038/SREP36874
Abstract: NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G C, located in a microRNA binding site in the 3′-untranslated region (UTR) of NBS1 , was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non- BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936–1.574, P = 0.144). Because we could not exclude a small effect size due to a limited s le size, we further analyzed imputed rs2735383 genotypes ( r 2 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969–1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905–1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.
Publisher: American Association for Cancer Research (AACR)
Date: 26-01-2021
DOI: 10.1158/1055-9965.EPI-20-0924
Abstract: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj & 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)] current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus & years at first pregnancy [0.79 (0.72–0.86)] & –& years versus ≥10 years since last full-term birth [1.31 (1.11–1.55)] ever versus never use of oral contraceptives [0.91 (0.87–0.96)] ever versus never use of menopausal hormone therapy, including current estrogen–progestin therapy [0.61 (0.54–0.69)]. Similar associations with breast cancer mortality were weaker for ex le, 1.11 (1.02–1.21) for current versus never smoking. We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
Publisher: Springer Science and Business Media LLC
Date: 17-06-2014
DOI: 10.1038/NCOMMS5051
Publisher: American Association for Cancer Research (AACR)
Date: 02-2022
DOI: 10.1158/1055-9965.EPI-21-0977
Abstract: There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects. This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. The prediagnosis inflammation-related exposures of interest included alcohol use aspirin use other nonsteroidal anti-inflammatory drug use body mass index environmental tobacco smoke exposure history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis menopausal hormone therapy use physical inactivity smoking status and talc use. Using Cox proportional hazards models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed, and its association with survival was assessed using Cox proportional hazards models in the remaining 50% of the data. There was a statistically significant trend of increasing risk of death per quartile of the IRRS [HR = 1.09 95% confidence interval (CI), 1.03–1.14]. Women in the upper quartile of the IRRS had a 31% higher death rate compared with the lowest quartile (95% CI, 1.11–1.54). A higher prediagnosis IRRS was associated with an increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether postdiagnosis exposures are also associated with survival. Given that pre- and postdiagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among patients with ovarian cancer.
Publisher: Springer Science and Business Media LLC
Date: 22-11-2019
DOI: 10.1038/S41598-019-53654-9
Abstract: Genome-wide association studies (GWAS) have successfully identified about 70 genomic loci associated with breast cancer. Owing to the complexity of linkage disequilibrium and environmental exposures in different populations, it is essential to perform regional GWAS for better risk prediction. This study aimed to investigate the genetic architecture and to assess common genetic risk model of breast cancer with 6,669 breast cancer patients and 21,930 female controls in the Japanese population. This GWAS identified 11 genomic loci that surpass genome-wide significance threshold of P 5.0 × 10 −8 with nine previously reported loci and two novel loci that include rs9862599 on 3q13.11 ( ALCAM ) and rs75286142 on 21q22.12 ( CLIC6-RUNX1 ). Validation study was carried out with 981 breast cancer cases and 1,394 controls from the Aichi Cancer Center. Pathway analyses of GWAS signals identified association of dopamine receptor medicated signaling and protein amino acid deacetylation with breast cancer. Weighted genetic risk score showed that in iduals who were categorized in the highest risk group are approximately 3.7 times more likely to develop breast cancer compared to in iduals in the lowest risk group. This well-powered GWAS is a representative study to identify SNPs that are associated with breast cancer in the Japanese population.
Publisher: Springer Science and Business Media LLC
Date: 15-06-2015
DOI: 10.1038/NG.3336
Publisher: Public Library of Science (PLoS)
Date: 30-09-2014
Publisher: Impact Journals, LLC
Date: 31-01-2016
Publisher: Spandidos Publications
Date: 23-06-2015
DOI: 10.3892/OL.2015.3414
Publisher: American Association for Cancer Research (AACR)
Date: 31-05-2017
DOI: 10.1158/0008-5472.CAN-16-2568
Abstract: Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case–control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A& C, p.Tyr3035Ser (OR = 2.52 P = 0.04), and BRCA1 c.5096G& A, p.Arg1699Gln (OR = 4.29 P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G& A, p.Gly2508Ser (OR = 2.68 P = 0.004), and c.8187G& T, p.Lys2729Asn (OR = 1.4 P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res 77(11) 2789–99. ©2017 AACR.
Publisher: Springer Science and Business Media LLC
Date: 02-10-2023
Publisher: Springer Science and Business Media LLC
Date: 07-07-2015
DOI: 10.1038/NCOMMS8138
Publisher: Oxford University Press (OUP)
Date: 23-06-2014
DOI: 10.1093/JNCI/DJU149
Publisher: Springer Science and Business Media LLC
Date: 20-07-2014
DOI: 10.1038/NG.3041
Publisher: Oxford University Press (OUP)
Date: 24-03-2015
DOI: 10.1093/HMG/DDV101
Publisher: BMJ
Date: 10-2013
DOI: 10.1136/BMJ.F5446
Publisher: American Association for Cancer Research (AACR)
Date: 31-08-2017
DOI: 10.1158/1055-9965.EPI-17-0367
Abstract: Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between in idual concurrent comorbidities and prognosis in ovarian cancer patients. Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis asthma depression osteoporosis and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes. Results: None of the comorbidities were associated with ovarian cancer outcome in the overall s le nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced). Conclusions: Histories of endometriosis asthma depression osteoporosis and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival. Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev 26(9) 1470–3. ©2017 AACR.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2015
DOI: 10.1038/NG.3242
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
Publisher: American Society of Hematology
Date: 10-2001
Publisher: Springer Science and Business Media LLC
Date: 07-11-2017
Publisher: Springer Science and Business Media LLC
Date: 29-02-2016
DOI: 10.1038/NG.3521
Publisher: Oxford University Press (OUP)
Date: 23-01-2023
DOI: 10.1093/JNCI/DJAD011
Abstract: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). In idual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.
Publisher: American Association for Cancer Research (AACR)
Date: 06-2014
DOI: 10.1158/1055-9965.EPI-13-0901
Abstract: Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using in idual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for “moderate drinkers” versus nondrinkers. An analysis of in idual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95 95% confidence interval (CI), 0.85–1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80 95% CI, 0.73–0.88). In idual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre- or postdiagnosis alcohol consumption is associated with breast cancer–specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer–specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer–specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer–specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. Cancer Epidemiol Biomarkers Prev 23(6) 934–45. ©2014 AACR.
Publisher: Springer Science and Business Media LLC
Date: 14-03-2017
Publisher: Oxford University Press (OUP)
Date: 22-01-2015
DOI: 10.1093/IJE/DYU255
Publisher: Elsevier BV
Date: 11-2015
Publisher: Wiley
Date: 21-01-2018
DOI: 10.1111/CAS.13470
Publisher: Springer Science and Business Media LLC
Date: 17-08-2017
DOI: 10.1038/BJC.2017.267
Publisher: American Association for Cancer Research (AACR)
Date: 02-2019
DOI: 10.1158/0008-5472.CAN-17-3864
Abstract: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene. See related commentary by Choi and Brown, p. 439
Publisher: Springer Science and Business Media LLC
Date: 20-12-2022
Publisher: Public Library of Science (PLoS)
Date: 19-06-2015
Publisher: Public Library of Science (PLoS)
Date: 06-07-2018
Publisher: Wiley
Date: 17-06-2016
DOI: 10.1002/IJC.30150
Publisher: Public Library of Science (PLoS)
Date: 22-04-2014
Publisher: Massachusetts Medical Society
Date: 24-02-2011
Publisher: Springer Science and Business Media LLC
Date: 23-10-2017
DOI: 10.1038/NATURE24284
Publisher: Springer Science and Business Media LLC
Date: 07-07-2015
DOI: 10.1038/BJC.2015.245
Publisher: Oxford University Press (OUP)
Date: 18-06-2014
DOI: 10.1093/HMG/DDU311
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: 10-2007
DOI: 10.1158/1078-0432.CCR-07-0216
Abstract: Purpose: Mutation of epidermal growth factor receptor (EGFR) gene has been reported to be present in non–small cell lung cancer (NSCLC) and significantly associated with female sex and never-smoking status. In this study, we extensively investigated the impact of sex and smoking on the EGFR mutation. Experimental Design: We examined EGFR exons 18 to 21 status in 1,467 NSCLC patients by direct sequencing to study the impact of sex and smoking status on the EGFR mutational spectrum. Results: Among 1,467 patients, 197 mutations were found at exon 19, 176 at exon 21, 21 at exon 18, and 24 at exon 20. To examine the independent effect of sex and smoking, the mutational status of each exon was compared between smokers and never smokers in each sex and between males and females stratified by smoking status. In females, exon 19 (P = 0.001) and exon 21 (P & 0.001) mutations were significantly less frequent in ever smokers compared with never smokers. In males, exon 19 (P & 0.001), exon 21 (P & 0.001), and exon 18 (P = 0.003) mutations were significantly less frequent in ever smokers compared with never smokers. In analysis stratified by smoking, there was no difference in sex among never smokers. However, exon 19 mutations were significantly less frequent in males compared with females among ever smokers (P = 0.003). In addition, the interactive effect of male sex and ever smoking status significantly decreased the frequency of exon 19 mutations (P = 0.047) when female never smoker was set as a reference. Conclusion: Both sex and smoking status could influence the EGFR mutational spectrum. Our findings suggest that in idual EGFR exons may have differing susceptibilities for mutagenesis.
Publisher: Springer Science and Business Media LLC
Date: 06-2016
DOI: 10.1038/BJC.2016.153
Publisher: Springer Science and Business Media LLC
Date: 12-01-2015
DOI: 10.1038/NG.3185
Publisher: Wiley
Date: 13-10-2021
DOI: 10.1002/IJC.33308
Publisher: Springer Science and Business Media LLC
Date: 29-08-2019
DOI: 10.1038/S41598-019-48804-Y
Abstract: Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC , has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1 , BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
Publisher: Public Library of Science (PLoS)
Date: 22-06-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 23-10-2017
DOI: 10.1038/NG.3785
Publisher: Public Library of Science (PLoS)
Date: 30-12-2016
Publisher: Springer Science and Business Media LLC
Date: 21-06-2016
Publisher: Public Library of Science (PLoS)
Date: 24-08-2016
Publisher: Elsevier BV
Date: 10-2016
Publisher: Wiley
Date: 28-08-2013
DOI: 10.1002/IJC.28402
No related grants have been discovered for Keitaro Matsuo.