| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Ferreira, MA, et al.
(författare)
-
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Antoniou, A. C., et al.
(författare)
-
Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
- 2010
-
Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
-
Tidskriftsartikel (refereegranskat)abstract
- The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Engel, C., et al.
(författare)
-
Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
- 2010
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:11, s. 2859-2868
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population.Methods: To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).Results: The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85; 95% CI, 0.76-0.97; Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; Ptrend = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers.Conclusions: CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers.Impact: The combined application of these and other recently identified genetic riskmodifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Ding, Yuan C, et al.
(författare)
-
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Mavaddat, N, et al.
(författare)
-
Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
- 2020
-
Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 22:1, s. 8-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.MethodsA multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.ResultsThere was no association between RRSO and breast cancer forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR forBRCA2mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.ConclusionWe found no evidence that RRSO reduces breast cancer risk forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
|
|
| 34. |
|
|
| 35. |
- Osorio, Ana, et al.
(författare)
-
DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
|
|
| 36. |
- Schmutzler, RK, et al.
(författare)
-
Risk-Adjusted Cancer Screening and Prevention (RiskAP): Complementing Screening for Early Disease Detection by a Learning Screening Based on Risk Factors
- 2022
-
Ingår i: Breast care (Basel, Switzerland). - : S. Karger AG. - 1661-3791 .- 1661-3805. ; 17:2, s. 208-223
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Risk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action. <b><i>Summary:</i></b> Therefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept.
|
|
| 37. |
- Schrijver, L, et al.
(författare)
-
Oral contraceptive use and breast cancer risk: A cohort study of BRCA1 and BRCA2 mutation carriers
- 2017
-
Ingår i: Cancer Research. - 1538-7445. ; 77:13 Suppl 1
-
Konferensbidrag (refereegranskat)abstract
- Background: BRCA1 and BRCA2 mutation carriers are at high risk of breast and ovarian cancer. Oral contraceptive preparations (OCPs) may reduce ovarian cancer risk, but its effect on breast cancer risk remains unclear. Methods: Combined data from three cohorts of 5705 BRCA1 and 3521 BRCA2 mutation carriers (IBCCS, BCFR and kConFab) were analyzed using age-dependent Cox regression models stratified for study and birth cohort. We conducted the first prospective analyses on this topic. Our additional main retrospective analyses were leftcensored 5 years preceding date of baseline questionnaire to control for survival bias. The full-cohort retrospective analyses, without left-censoring, was performed to compare results with the literature. Prospective analyses were considered most valid, while retrospective analyses were most powerful. Results: For BRCA1 mutation carriers we found no association between ever OCP use and risk of breast cancer in the prospective analyses (HR=1.08, 95% CI 0.75-1.56), but 23% and 27% increased risks for ever OCP use in the left-censored and full retrospective analyses, respectively. Retrospectively, an increasing trend for longer duration of use, especially before first full-term pregnancy (FFTP) was found (left-censored analyses: 10 years HR 1.41 (95%CI 1.10-1.813), p-trend=0.001 for duration of use before FFTP). For BRCA2 mutation carriers we found a positive association between ever OCP use and risk of breast cancer prospectively (HR=1.75, 95% CI 1.03-2.97), but retrospectively findings were inconsistent (HR=1.06, 95% CI 0.85-1.33 and HR=1.52, 95% CI 1.28-1.81 for the left-censored and full analyses, respectively). Conclusion: For BRCA1 mutation carriers the discrepancy between results of prospective and retrospective analyses may be explained by time since last OCP use before FFTP. Thus, a temporal increased risk of breast cancer following longer duration of OCP use before FFTP cannot be ruled out. The discordant findings between prospective and retrospective analyses for BRCA2 carriers could not be explained. Because of the lack of scientific clarity it is too early to give an unequivocal advice on OCP use with respect to breast cancer risk to BRCA1 and BRCA2 mutation carriers.
|
|
| 38. |
- Vigorito, Elena, et al.
(författare)
-
Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
-
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.
|
|
| 39. |
- Antoniou, Antonis C., et al.
(författare)
-
Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
-
Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
|
|
| 40. |
- Hemminki, Kari, et al.
(författare)
-
Low-risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer patients
- 2010
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:12, s. 2858-2862
-
Tidskriftsartikel (refereegranskat)abstract
- To validate common low-risk variants predisposing for breast cancer (BC) in a large set of BRCA1/2 negative familial or genetically enriched cases from Germany, we genotyped 1,415 cases and 1,830 healthy women by MALDI-TOF in 105 candidate SNPs. Significantly higher ORs than previously reported for heterozygous unselected cases were found for the minor allele in FGFR2 (OR = 1.43, 95% Cl 1.30-1.59, p-value = 1.24 x 10(-12)) and for TNRC9 (OR = 1.33, 95% Cl 1.19-1.46, p-value = 1.54 x 10(-7)). Most intriguing, however, were the ORs for homozygous carriers from high-risk families for FGFR2 (OR = 2.05, 95% Cl 1.68-2.51, LSP1 (OR = 0.49, 95% Cl 0.28-0.86) and TNRC9 (OR = 1.62, 95% Cl 1.27-2.07). Moreover, the additional validation of 99 CGEMS-SNPs identified putative novel susceptibility alleles within the LSP1 gene (OR = 0.73, 95% Cl 0.61-0.87, p-value = 5.23 x 10(-4)). Finally, we provide evidence for the first time that a low-risk variant located at 6q22.33 (rs6569479) is associated with estrogen receptor negative BC in familial cases (OR = 1.33, 95% Cl 1.06-1.66; p-value = 0.012). Our data confirm the impact of the previously identified susceptibility loci and provide preliminary evidence for novel susceptibility loci in familial BC cases and correlate them to specific histopathological subtypes defined by estrogen receptor status.
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Schrijver, Lieske H, et al.
(författare)
-
Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers : an international cohort study
- 2021
-
Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 225:1, s. 1-51
-
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.
|
|
| 44. |
|
|
