Common mutations in BRCA1 and BRCA2 do not contribute to early prostate cancer in Jewish men

BACKGROUND. Families with a high incidence of hereditary breast cancer, and subsequently shown to have terminating mutations in BRCA1 or BRCA2, appear to have a higher incidence of prostate cancer among male relatives. We aim ed to determine whether the common germline mutations of BRCA1 or BRCA2 in Ashkenazi Jewish men predisposed them to prostate cancer. METHODS. We examined genomic DNA from 83 (for BRCA1 185delAC) or 82 (for BR CA2 6174delT) Ashkenazi Jewish prostate cancer patients, most of whom were treated at a relatively young age, for the most common germline mutation in each gene seen in the Ashkenazi population RESULTS. Our study should have been able to detect a 4-5-fold increase in t he risk of prostate cancer due to mutation of BRCA1 or BRCA2. However, only one (1.15%; 95% confidence interval, 0-3.6%) of the patients was heterozyg ous for the BRCA1 mutant allele, and only two were heterozygous for the BRC A2 mutation (2.4%; 95% confidence interval, 0-6.2%). CONCLUSIONS. The incidence of each of the germline mutations in these prost ate cancer patients closely matched their incidence (about 1%) in the gener al Ashkenazi Jewish population. This suggests that unlike cases of breast a nd ovarian cancers, mutations in BRCA1 or BRCA2 do not significantly predis pose men to prostate cancer. (C) 1999 Wiley-Liss, Inc.