Prevalence and type of BRCA mutations in Hispanics undergoing genetic cancer risk assessment in the southwestern United States: a report from the Clinical Cancer Genetics Community Research Network

Abstract

Purpose: To determine the prevalence and type of BRCA1 and BRCA2 (BRCA) mutations among Hispanics in the Southwestern United States and their potential impact on genetic cancer risk assessment (GCRA).

Patients and methods: Hispanics (n = 746) with a personal or family history of breast and/or ovarian cancer were enrolled in an institutional review board-approved registry and received GCRA and BRCA testing within a consortium of 14 clinics. Population-based Hispanic breast cancer cases (n = 492) enrolled in the Northern California Breast Cancer Family Registry, negative by sequencing for BRCA mutations, were analyzed for the presence of the BRCA1 ex9-12del large rearrangement.

Results: Deleterious BRCA mutations were detected in 189 (25%) of 746 familial clinic patients (124 BRCA1, 65 BRCA2); 21 (11%) of 189 were large rearrangement mutations, of which 62% (13 of 21) were BRCA1 ex9-12del. Nine recurrent mutations accounted for 53% of the total. Among these, BRCA1 ex9-12del seems to be a Mexican founder mutation and represents 10% to 12% of all BRCA1 mutations in clinic- and population-based cohorts in the United States.

Conclusion: BRCA mutations were prevalent in the largest study of Hispanic breast and/or ovarian cancer families in the United States to date, and a significant proportion were large rearrangement mutations. The high frequency of large rearrangement mutations warrants screening in every case. We document the first Mexican founder mutation (BRCA1 ex9-12del), which, along with other recurrent mutations, suggests the potential for a cost-effective panel approach to ancestry-informed GCRA.

Fig 1.

Mutation screening outcomes (A) among the high-risk clinic study population; (B) among the Northern California site of the Breast Cancer Family Registry (NC-BCFR). BART, BRCA Analysis Rearrangement Testing; NCCN, National Comprehensive Cancer Network; VUS, variant of uncertain significance. (*) BART (Myriad Genetics Laboratory, Salt Lake City, UT) performed on 200 cases (34 automatic/166 elective); multiplex ligation-dependent probe amplification of BRCA1 performed on 345 cases; no DNA available for 20 cases.

Fig 2.

Graphical comparison of recurrent mutations across three Hispanic cohorts: (1) Current study population, Weitzel et al, (2) Texas population, Vogel et al, and (3) California population, John et al *The C1787S mutation is actually two adjacent missense mutations: C1787S and G1788D.