Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers
Purpose
Mutations in BRCA1/2
dramatically increase the risk of both breast and ovarian cancers.
Three mutations in these genes (185delAG, 5382insC, and
6174delT) occur at high frequency in Ashkenazi
Jews. We evaluated how these common Jewish mutations (CJMs) affect
cancer risks
and risk reduction.
Methods
Our cohort comprised 4,649 women with disease-associated BRCA1/2
mutations from 22 centers in the Prevention and Observation of Surgical
End Points Consortium. Of these women, 969 were self-identified
Jewish women. Cox proportional hazards models
were used to estimate breast and ovarian cancer risks, as well as risk
reduction
from risk-reducing salpingo-oophorectomy (RRSO),
by CJM and self-identified Jewish status.
Results
Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively). Relative risks of cancer varied by CJM, with the relative risk
of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers. No significant difference was seen in cancer risk reduction after RRSO
among subgroups.
Conclusion
Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation
in larger prospective and population-based cohort studies before being integrated into clinical care.