The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer

Predisposition to prostate cancer has a genetic component, and there are re ports of familial clustering of breast and prostate cancer. Two highly pene trant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold an d 7-fold, respectively, in breast cancer families. Blood DNA from affected individuals in 38 prostate cancer clusters was analyzed for germline mutati ons in BRCA1 and BRCA2 to assess the contribution of each of these genes to familial prostate cancer. Seventeen DNA samples were each from an affected individual in families with three or more cases of prostate cancer at any age; 20 samples were from one of affected sibling pairs where one was less than or equal to 67 years at diagnosis, No germ-line mutations were found i n BRCA1. Two germ-line mutations in BRCA2 were found, and both were seen in individuals whose age at diagnosis was very young (less than or equal to 5 6 years) and who were members of an affected sibling pair. One is a 4-bp de letion at base 6710 (exon 11) in a man who had prostate cancer at 54 Sears, and the other is a 2-bp deletion at base 5531 (ex:on 11) in a man who had prostate cancer at 56 years, In both cases, the wild-type allele was lost i n the patient's prostate tumor at the BRCA2 locus. However, intriguingly, i n neither case did the affected brother also carry the mutation. Germ-line mutations in BRCA2 may therefore account for about 5% of prostate cancer in familial clusters.