The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel

Inherited predisposition occurs in 5-10% of all prostate cancer (CaP) patie nts, but the genes involved in conferring genetic susceptibility remain lar gely unknown. Several lines of evidence indicate that germline mutations in BRCA1 and BRCA2 might be associated with an increased risk for CaP. Th ree mutations in these two genes (185delAG and 5382InsC (BRCA1) and 6174delT ( BRCA2) occur in about 2.5% of the general Ashkenazi population, and the 185 delAG BRCA1 mutation, in up to 1% of non-Ashkenazi Jews. In order to assess the contribution of these germline mutations to prostate cancer in Jewish Israeli patients, we tested 174 unselected prostate cancer patients (95 of Ashkenazi origin) for these mutations by PCR amplification and modified res triction enzyme digests. Patient's age range was 45-81 years (median 66), a nd in 24 (14.4%) the disease was diagnosed prior to 55 years of age. Ninete en (11%) and 12 (6.9%) patients had a first or second degree relative with CaP or breast cancer, respectively. Overall, five mutation carriers were de tected: 2/152 (1.3%) 185delAG, 2/104 (2%) 5382InsC, and 1/158 (0.6%) 6174de lT. in all carriers, the disease was diagnosed after the age of 55, and onl y one of them had a family history of breast and CaP. In addition, no allel ic losses at the BRCA1 locus were demonstrated in 17 patients with a family history of CaP, using seven microsatellite markers. We conclude that the r ate of the predominant Jewish BRCA1 and BRCA2 mutations in CaP patients doe s not significantly differ from that of the general population, and that mu tational inactivation of the BRCA1 is rare in familial CaP. Thus, germline BRCA1 and BRCA2 mutations probably contribute little to CaP occurrence, to inherited predisposition, and to early onset disease in Jewish individuals. (C) 2000 Cancer Research Campaign.