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Departments of 1 Clinical Cancer Genetics and 2 Information Sciences, City of Hope Cancer Center, Duarte, California; 3 Cancer Risk Program, St. Joseph Hospital Regional Cancer Center, Orange, California; and 4 Division of Epidemiology, Department of Medicine, University of California Irvine, Irvine, California
Requests for reprints: Jeffrey N. Weitzel, Department of Clinical Cancer Genetics, City of Hope Cancer Center, 1500 East Duarte Road, Mod 103, Duarte, CA 91010. Phone: 626-256-8662; Fax: 626-930-5495. E-mail: jweitzel{at}coh.org
Approximately 12% of the U.S. population is Hispanic, with the majority residing in urban centers such as Los Angeles. The prevalence of BRCA mutations among high-risk Hispanic families is unknown.
Methods: One hundred and ten unrelated probands ofHispanicorigin, with a personal or family history of breast and/orovarian cancer, presented for genetic cancer risk assessment, were enrolled in an Institutional Review Board–approved registry and underwent BRCA testing. Haplotype analyseswere done if BRCA mutations were observed in two or more unrelated probands.
Results: Mean age at diagnosis was 37 years (range = 23-59) for the 89 (81%) probands with invasive breast cancer. Overall, 34 (30.9%) had deleterious mutations (25 in BRCA1, 9 in BRCA2), 25 (22.7%) had one or more unclassified variants, and 51 (46.4%) had negative results. The mean pretest mutation probability using the Couch model, Myriad model, and BRCAPro was 19.6% (range = 4-77%). The combined average mutation probability was 32.8% for carriers, 15.5% for noncarriers, and 12.9% for variant carriers (P < 0.0001). The most common deleterious mutation was 185delAG (4 of 34, 11.8%). The Hispanic 185delAG carrier families share the same haplotype from D17s1320 through BRCA1, as do two reference Ashkenazi Jewish families. Haplotype analyses ofadditional recurrent BRCA1 mutations [IVS5+1G>A (n=2),S955X (n = 3), R1443X (n = 3), and 2552delC (n = 2)] also suggest founder effects, with four of six mutations seenalmost exclusively in families with Latin American/Caribbean or Spanish ancestry.
Conclusion: This is the largest study to date of high-risk Hispanic families in the United States. Six recurrent mutations accounted for 47% (16 of 34) of the deleterious mutations in this cohort. The BRCA1185delAG mutation wasprevalent (3.6%) in this clinic-based cohort of predominantly Mexican descent, and shared the Ashkenazi Jewishfounder haplotype.
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