No evidence for a role of BRCA1 or BRCA2 mutations in Ashkenazi Jewish families with hereditary prostate cancer

BACKGROUND. Two genes responsible for hereditary breast cancer (BRCA1 and B ACA2) have been identified, and predisposing mutations identified. Several studies have provided evidence that germline mutations in BRCA1 and BRCA2 c onfer an increased risk of prostate cancer. Based on these findings, one mi ght expect to find an increased frequency of mutations in these genes in fa mily clusters of prostate cancer. The Ashkenazi Jewish population is unique in that it has an approximate 2% incidence of specific founder BRCA1 and B RCA2 mutations (i.e., 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2 ). METHODS. To address the question of whether or not mutations in either of t hese genes were overrepresented in prostate cancer families, we searched fo r these mutations in germline DNA samples collected from affected and unaff ected members of 18 Ashkenazi Jewish families, each having at least 3 first -degree relatives affected with prostate cancer. RESULTS. No mutations were found in the BRCA1 gene in any of the 47 individ uals tested. One individual possessed a BRCA2 mutation (6174delT). This ind ividual was unaffected at the time of analysis, but had an affected paterna l uncle,: and an affected first cousin, neither of whom harbored the mutant gene. CONCLUSIONS. In this sample of Ashkenazi prostate cancer families, the freq uency of founder BRCA1 and BRCA2 mutations was not elevated, suggesting tha t such mutations will account for only a small, perhaps minimal, fraction o f familial prostate cancer. (C) 1999 Wiley-Liss, Inc.