BRCA1 and BRCA2 mutations in a study of African American breast cancer patients.

The spectrum of mutations in BRCA1 and BRCA2 among African Americans has not been well characterized because most studies to date have been done in Caucasian families. According to Myriad Genetic Laboratories, Inc., only approximately 3% of individuals undergoing BRCA1/BRCA2 testing reported African American ancestry. Data from previous studies show that among African American women a greater proportion of breast cancer cases are diagnosed at age <45 years in comparison with Caucasians. Because breast cancer occurring at a young age is one of the hallmarks of high penetrance genes, the prevalence, spectrum, and effects of BRCA1/BRCA2 mutations may differ substantially between African Americans and Caucasians, and further investigation is warranted. We conducted a hospital-based study of African American breast cancer patients with early age at diagnosis (</=45 years) or family history of breast or ovarian cancer. We identified four deleterious mutations in BRCA1 or BRCA2 among the 10 families tested, of which two were novel BRCA2 mutations, one was the west African founder mutation (BRCA1 943ins10), and one was a recurrent mutation that may be a candidate for a second African American founder mutation (BRCA1 IVS13+1G>A). Our results support previous data in demonstrating that (a) the spectrum of mutations among African Americans is unique, (b) family history of breast cancer is an important predictor of hereditary cancer susceptibility among African Americans, and (c) empirical data may be useful in estimating mutation risk among African Americans.