title: 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: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: City of Hope, Duarte, CA 91010, USA. jweitzel@coh.org
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weitzel
authors.forename: Jessica
authors.initials: J
authors.lastname: Clague
authors.forename: Arelis
authors.initials: A
authors.lastname: Martir-Negron
authors.forename: Raquel
authors.initials: R
authors.lastname: Ogaz
authors.forename: Josef
authors.initials: J
authors.lastname: Herzog
authors.forename: Charité
authors.initials: C
authors.lastname: Ricker
authors.forename: Chelsy
authors.initials: C
authors.lastname: Jungbluth
authors.forename: Cheryl
authors.initials: C
authors.lastname: Cina
authors.forename: Paul
authors.initials: P
authors.lastname: Duncan
authors.forename: Gary
authors.initials: G
authors.lastname: Unzeitig
authors.forename: J Salvador
authors.initials: JS
authors.lastname: Saldivar
authors.forename: Mary
authors.initials: M
authors.lastname: Beattie
authors.forename: Nancy
authors.initials: N
authors.lastname: Feldman
authors.forename: Sharon
authors.initials: S
authors.lastname: Sand
authors.forename: Danielle
authors.initials: D
authors.lastname: Port
authors.forename: Deborah I
authors.initials: DI
authors.lastname: Barragan
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Garrett P
authors.initials: GP
authors.lastname: Larson
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D015995:Prevalence; D015206:Southwestern United States / Q000453:epidemiology