© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 14, 1241-1247,
July 21, 1999
© 1999 Oxford University Press
REPORTS |
Prevalence and Penetrance of BRCA1 and BRCA2 Gene Mutations in Unselected Ashkenazi Jewish Women With Breast Cancer
Affiliations of authors: E. Warner, L. Di Prospero, Division of Medical Oncology, Toronto-Sunnybrook Regional Cancer Centre, ON, Canada; W. Foulkes, N. Hamel, C. Serruya, Cancer Prevention Unit, Sir Mortimer B. Davis-Jewish General Hospital, and Montreal General Hospital Research Institute, McGill University, Montreal, PQ, Canada; P. Goodwin, V. Contiga (Marvelle Koffler Breast Centre), H. Ozcelik (Samuel Lunenfeld Research Institute), Mount Sinai Hospital, Toronto; W. Meschino, D. Allingham-Hawkins, J. Honeyford, Department of Medical Genetics, North York General Hospital, Toronto; J. Blondal, C. Paterson, R. Moslehi, A. Liede, J.-S. Brunet, S. Narod, Centre for Research on Women's Health, Women's College Hospital, Toronto; P. Goss, M. Klein, Division of Medical Oncology, The Toronto Hospital; G. Glendon, Ontario Cancer Genetics Network.
Correspondence to: Ellen Warner, M.D., M.Sc., FRCPC, FACP, Division of Medical Oncology, Toronto-Sunnybrook Regional Cancer Centre, 2075 Bayview Ave., Toronto, ON M4N 3M5 Canada (e-mail: ellen_warner{at}cancercare.on.ca).
BACKGROUND: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8.48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1.49-7.56). CONCLUSIONS: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.
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