| 11. |
- Schrijver, Lieske H, et al.
(författare)
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Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers : an international cohort study
- 2021
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 225:1, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive preparations (OCPs) use. While the effects of OCPs in the general population are well established (∼50% reduction), the estimated risk reduction in mutation carriers is much less precise due to potential bias and small sample sizes. In addition, only a few studies have examined the associations between duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer.OBJECTIVE(S): To investigate in more detail the associations between various characteristics of OCP use and risk of ovarian cancer, to provide health care providers and carriers with better risk estimates.STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using OCP data on 3,989 BRCA1 and 2,445 BRCA2 mutation carriers. Age-dependent weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as covariate. To minimize survival bias, analyses were left-truncated at 5 years before baseline questionnaire. Separate analysis were conducted for each of the aspects of OCP use and in a multivariate analysis including all these aspects. In addition, the analysis of duration of OCP use was stratified by recency of use.RESULTS: OCPs were less often used by mutation carriers who were diagnosed with ovarian cancer (Ever use: BRCA1 58.6%, BRCA2 53.5%) than by unaffected carriers (Ever use: BRCA1 88.9%, BRCA2 80.7%. The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer, and 9 and 8 years for ovarian cancer unaffected BRCA1 and BRCA2 carriers, respectively. For BRCA1 mutation carriers univariate analyses showed that both a longer duration of OCP use and more recent use of OCPs were inversely associated with risk of ovarian cancer. However, in multivariate analyses including duration of use, age at first use and time since last use, duration of use proved to be the prominent protective factor (compared with <5 years, 5-9 years HR=0.67;95%CI 0.40-1.12, 10+ years HR=0.37;95%CI 0.19-0.73; ptrend=0.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (Duration of ≥10 years; BRCA1: <15 years since last use: HR=0.24 95%CI 0.14-0.43, 15+ years since last use: HR 0.56 95%CI 0.18-0.59). Univariate results for BRCA2 mutation carriers were similar, but due to limit sample size inconclusive.CONCLUSION: For BRCA1 mutation carriers, a longer duration of OCP use is associated with a greater reduction of ovarian cancer risk and the protection is long term.
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| 12. |
- Spurdle, Amanda B., et al.
(författare)
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Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers
- 2011
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 20:5, s. 1032-1038
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR.
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| 13. |
- Teerlink, Craig C., et al.
(författare)
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Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease
- 2014
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Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 133:3, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p a parts per thousand currency sign 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.
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| 14. |
- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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| 15. |
- Walker, Logan C, et al.
(författare)
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Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers.
- 2010
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X .- 1465-5411. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies.
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