title: Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations.
abstract: Germline mutations in BRCA1 or BRCA2 (BRCA) are responsible for 5-15% of breast (BC) and ovarian cancers (OC), predisposing to the development of early onset and often multiple primary tumors. Since mutation carriers can benefit from risk-reducing interventions, the identification of individuals with hereditary breast and ovarian cancer (HBOC) syndrome has a significant clinical impact. We assessed whether a panel assay for recurrent Hispanic BRCA mutations (HISPANEL) has an adequate breadth of coverage to be suitable as a cost effective screening tool for HBOC in a cohort of patients from Southern Brazil. A multiplex, PCR-based panel was used to genotype 232 unrelated patients for 114 germline BRCA mutations, finding deleterious mutations in 3.5% of them. This mutation prevalence is within the range detected by the HISPANEL among BC patients unselected for family history in other Latin American settings. The HISPANEL would have accounted for 27% of the BRCA mutations detected by complete sequencing in a comparison cohort (n = 193). This prevalence may be region-specific since significant differences in population structure exist in Brazil. Comprehensive analysis of BRCA in a larger set of HBOC patients from different Brazilian regions is warranted, and the results could inform customization of the HISPANEL as an affordable mutation screening tool.
authors.affiliation: Programa de Pós-graduação em Genética e Biologia Molecular (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500-Prédio 43323M, Porto Alegre, Rio Grande do Sul 91501-970, Brazil; Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, Rio Grande do Sul 90035-903, Brazil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Alemar
authors.affiliation: Department of Population Sciences, Division of Clinical Cancer Genetics, City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Josef
authors.initials: J
authors.lastname: Herzog
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, Rio Grande do Sul 90035-903, Brazil.
authors.forename: Cristina
authors.initials: C
authors.lastname: Brinckmann Oliveira Netto
authors.affiliation: Hospital Moinhos de Vento (HMV), Rua Ramiro Barcelos, 910, Porto Alegre, Rio Grande do Sul 91790-560, Brazil.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Artigalás
authors.affiliation: Programa de Pós-graduação em Genética e Biologia Molecular (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500-Prédio 43323M, Porto Alegre, Rio Grande do Sul 91501-970, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, Rio Grande do Sul 90035-903, Brazil; Departamento de Genética, UFRGS, Av. Bento Gonçalves, 9500-Prédio 43323M, Porto Alegre, Rio Grande do Sul 91501-970, Brazil.
authors.forename: Ida Vanessa D
authors.initials: IVD
authors.lastname: Schwartz
authors.affiliation: Programa de Pós-graduação em Genética e Biologia Molecular (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500-Prédio 43323M, Porto Alegre, Rio Grande do Sul 91501-970, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Matzenbacher Bittar
authors.affiliation: Programa de Pós-graduação em Genética e Biologia Molecular (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500-Prédio 43323M, Porto Alegre, Rio Grande do Sul 91501-970, Brazil; Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, Rio Grande do Sul 90035-903, Brazil; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, Porto Alegre, Rio Grande do Sul 90035-903, Brazil; Departamento de Genética, UFRGS, Av. Bento Gonçalves, 9500-Prédio 43323M, Porto Alegre, Rio Grande do Sul 91501-970, Brazil. Electronic address: pprolla@gmail.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
authors.affiliation: Department of Population Sciences, Division of Clinical Cancer Genetics, City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weitzel
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006630:Hispanic or Latino; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D055815:Young Adult
keywords: BRCA1; BRCA2; Hereditary breast and ovarian cancer