Prevalence of BRCA Mutations and Founder Effect in High-Risk Hispanic Families

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 His-panic families is unknown. Methods: One hundred and ten unrelated probands of His-panic origin, with a personal or family history of breast and/ or ovarian cancer, presented for genetic cancer risk assessment, were enrolled in an Institutional Review Board–approved registry and underwent BRCA testing. Haplotype analyses were 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 deleteriou