FREQUENCY AND CARRIER RISK ASSOCIATED WITH COMMON BRCA1 AND BRCA2 MUTATIONS IN ASHKENAZI JEWISH BREAST-CANCER PATIENTS

Based on breast cancer families with multiple and/or early-onset cases , estimates of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may be as high as 85%. The risk for individuals no t selected for family history or other risk factors is uncertain.We de termined the frequency of the common BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268 anonymous Ashkenazi Jew ish women with breast cancer, regardless of family history or age at o nset. DNA was analyzed for the three mutations by allele-specific olig onucleotide hybridization. Eight patients (3.0%, 95% confidence interv al [CI] 1.5%-5.8%) were heterozygous far the 185delAG mutation, two (0 .75%, 95% CI 0.20-2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT mutation. The lifetime risk for breast c ancer in Ashkenazi Jewish carriers of the BRCA1 185delAG or BRCA2, 617 4delT mutations was calculated to be 36%, approximately three times th e overall risk for the general population (relative risk 2.9, 95% CI 1 .5-5.8). For the 5382insC mutation, because of the low number of carri ers found, further studies are necessary. The results differ markedly from previous estimates based on high-risk breast cancer families and are consistent with lower estimates derived from a recent population-b ased study in the Baltimore area. Thus, presymptomatic screening and c ounseling for these common mutations in Ashkenazi Jewish women not sel ected for family history of breast cancer should be reconsidered until the risk associated with these mutations is firmly established, espec ially since early diagnostic and preventive-treatment modalities are l imited.