Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers

Brian S. Finkelman, Wendy S. Rubinstein, Sue Friedman, Tara M. Friebel, Shera Dubitsky, Niecee Singer Schonberger, Rochelle Shoretz, Christian F. Singer, Joanne L. Blum, Nadine Tung, Olufunmilayo I. Olopade, Jeffrey N. Weitzel, Henry T. Lynch, Carrie Snyder, Judy E. Garber, Joellen Schildkraut, Mary B. Daly, Claudine Isaacs, Gabrielle Pichert, Susan L. NeuhausenFergus J. Couch, Laura Van't Veer, Rosalind Eeles, Elizabeth Bancroft, D. Gareth Evans, Patricia A. Ganz, Gail E. Tomlinson, Steven A. Narod, Ellen Matloff, Susan Domchek, Timothy R. Rebbeck

    Research output: Contribution to journalArticlepeer-review


    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; odds ratio, 1.87; 95% CI, 1.44 to 2.42). 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 (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). 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. © 2012 by American Society of Clinical Oncology.
    Original languageEnglish
    Pages (from-to)1321-1328
    Number of pages7
    JournalJournal of Clinical Oncology
    Issue number12
    Publication statusPublished - 20 Apr 2012


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