Dataset Information

No sib pair concordance for breast or ovarian cancer in BRCA1 mutation carriers.

ABSTRACT: Modifying factors might theoretically determine whether a BRCA1 mutation carrier contracts breast or ovarian cancer. If so, one would expect concordance for breast or ovarian cancer in affected sibships. We identified 64 pairs with cancers where one or both sisters were demonstrated to carry a BRCA1 mutation, and 116 additional constructed pairs in sibships with three or more affected sisters. We analysed concordance for breast and for ovarian cancer both in the complete series and in the 64 sister pairs alone. The results were that concordance for both breast and ovarian cancer in sisters was in keeping with random distribution or multiple and frequent modifying genetic factors. In conclusion, there may be no major modifying factor of expression of BRCA1 mutations. The practical implication of our findings is that previous disease manifestations in close relatives may have no bearing on the first cancer to be expected in a young female mutation carrier.

SUBMITTER: Moller P

PROVIDER: S-EPMC2736994 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

No sib pair concordance for breast or ovarian cancer in BRCA1 mutation carriers.

Møller Pål P Maehle Lovise L Clark Neal N Apold Jaran J

Hereditary cancer in clinical practice 20070615 2

Modifying factors might theoretically determine whether a BRCA1 mutation carrier contracts breast or ovarian cancer. If so, one would expect concordance for breast or ovarian cancer in affected sibships. We identified 64 pairs with cancers where one or both sisters were demonstrated to carry a BRCA1 mutation, and 116 additional constructed pairs in sibships with three or more affected sisters. We analysed concordance for breast and for ovarian cancer both in the complete series and in the 64 sis ...[more]

PMID: 19725986

Similar Datasets

Project description:BackgroundGenome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates.MethodsWe constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS.ResultsThe PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2×10 -53 ). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2×10 -20 ). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS.ConclusionsBC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management.

Dataset Information

No sib pair concordance for breast or ovarian cancer in BRCA1 mutation carriers.

Publications

No sib pair concordance for breast or ovarian cancer in BRCA1 mutation carriers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets