Mohammad Akbari

The risks of breast and ovarian cancer associated with the Ashkenazi Jewish founder allele BRCA2 6174delT

Abstract Approximately 1% of the Ashkenazi Jewish population carries the BRCA2 6174delT (c.5946del) pathogenic variant. It is important to have accurate knowledge of the risks of breast and ovarian cancer associated with this specific variant so that women may be counseled accordingly. In this prospective study, we estimated the risks of breast and ovarian cancer associated with the 6174delT variant compared with the risks for other pathogenic variants in the BRCA2 gene. The annual risk for developing breast cancer was significantly lower in 246 women who carried the 6174delT variant compared with 721 non‐Jewish women who carried a variant at any other locus in BRCA2 (1.2% per year vs. 2.4% per year, p  = 0.003). We estimated the cumulative risk of breast cancer from age 30 to 70 to be 39% for carriers of the BRCA2 6174delT variant and 61% for carriers of other BRCA2 variants. The annual risk for ovarian or fallopian tube cancer was 0.51% per year for the 233 women who carried the 6174delT variant compared to 0.22% per year for the 1128 carriers of other BRCA 2 variants; the difference was not significant. Lower risks for breast cancer associated with 6174delT may not impact screening and prevention choices, however, the discussion should be based on accurate risk assessment.