Cancers Associated With BRCA1 and BRCA2 Mutations Other Than Breast and Ovarian

BACKGROUNDPrevious studies have reported additional cancers associated with BRCA mutations; however, the type, magnitude of risk, and sex differences remain to be clarified. The purpose of this study was to evaluate the incidence of cancers other than breast and ovarian cancer in known mutation carriers. METHODSAn institutional review board-approved study identified 1072 patients who had genetic counseling at the authors' institution and tested positive for a deleterious BRCA mutation. The expected number of cancer cases was calculated from the number of individuals in the study sample multiplied by the cancer incidence rates for the general population. The expected and observed numbers of cases were calculated in 5-year intervals to accommodate different age-related incidence rates. Standardized incidence ratios (SIRs) for each cancer type were calculated. RESULTSAmong the 1072 mutation carriers, 1177 cancers of 30 different cancer types were identified. Individuals with a BRCA1 mutation did not have a significant increase in cancers other than breast and ovarian cancer; however, a trend in melanoma was observed. Individuals with a BRCA2 mutation had significantly higher numbers of observed cases versus expected cases for pancreatic cancer in both men and women (SIR, 21.7; 95% confidence interval [CI], 13.1-34.0; P<.001) and for prostate cancer in men (SIR, 4.9; 95% CI, 2.0-10.1; P=.002). CONCLUSIONSThe results of this study uphold the current recommendations for hereditary breast and ovarian cancer screening of cancers other than breast and ovarian cancer by the National Comprehensive Cancer Network. Larger cohorts and collaborations are needed to further verify these findings. Cancer 2015;121:269-75. (c) 2014 American Cancer Society. In a cohort of more than 1000 known mutation carriers, BRCA2 mutations are associated with a higher rate of pancreatic cancer than previously reported. Increases have also been observed in prostate cancer and melanoma.