Nature Genetics
13, 126 - 128 (1996)
doi:10.1038/ng0596-126
Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancerSusan Neuhausen5, Teresa Gilewski3, Larry Norton3, Thao Tran5, Peter McGuire1, Jeff Swensen5, Heather Hampel1, Patrick Borgen4, Karen Brown1, Mark Skolnick6, 7, Donna Shattuck-Eidens6, Suresh Jhanwar2, David Goldgar7
& Kenneth Offit1, 8
1Clinical Genetics Service, Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York New, York, 10021, USA
2Cytogenetics Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York New, York, 10021, USA
3Breast Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York New, York, 10021, USA
4Breast Service, Department of Surgery Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York New, York, 10021, USA
5Genetic Epidemiology Group, Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City, Utah, 84108, USA
6Myriad Genetics, Inc., Salt Lake City, Utah, 84108, USA
7Unit of Genetic Epidemiology, International Agency for Research on Cancer, 150 cours Albert Thomas, 63972, Lyon, Cedex 08, France
8Correspondence should be addressed to K.O. The lifetime risk of breast cancer may approach 80−90% in women who have germline mutations of either of two genes, BRCA1 or BRCA2 (refs. 1−3). A single BRCA1 mutation, 185delAG, has been noted in approximately 20% of Ashkenazi Jewish women with early onset breast cancer and in 0.9% of the Ashkenazi population4−6. We recently detected a 6174delT frameshift mutation in BRCA2 in an hereditary breast cancer kindred of Ashkenazi Jewish ancestry. Here, we investigated the frequency of this mutation in 200 women with early-onset breast cancer. Six of 80 Ashkenazi Jewish women (8%) diagnosed with breast cancer before the age of 42, were heterozygous for the 6174delT mutation, compared to none of 93 non-Jewish women diagnosed with breast cancer at the same age (P = .005). These cases were ascertained without regard to family history. Two of 27 (7%) additional Jewish families in which the proband was diagnosed with breast cancer at age 42 to 50 and had a family history of breast or ovarian cancer had germline 6174delT mutations. The results of this report suggest that a recurrent mutation of BRCA1 and a recurrent mutation of BRCA2 together may account for over a quarter of all early-onset breast cancer cases and two thirds of early-onset breast cancer in the setting of a personal or family history of ovarian cancer in Ashkenazi Jewish women.
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