title: High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia.
abstract: In South America, a high proportion of the population is of Hispanic origin with an important representation in Colombia. Since nothing is known about the contribution of BRCA1 and BRCA2 germline mutations to hereditary breast/ovarian cancer in the Hispanic population from Colombia, we conducted the first study of 53 breast/ovarian cancer families from this country. Comprehensive BRCA mutation screening was performed using a range of techniques, including DHPLC, SSCP, and PTT, followed by DNA sequencing analysis. Thirteen deleterious germline mutations (24.5%) were identified in 53 families, comprising eight in BRCA1 and five in BRCA2. The two recurrent BRCA1 mutations, 3450 delCAAG and A1708E, accounted for 100% of all BRCA1 mutations identified in this cohort and the recurrent 3034 delACAA BRCA2 mutation for 40% of all BRCA2 mutations. Haplotype analyses suggested that each of these mutations has arisen from a common ancestor. The prevalence of BRCA1 or BRCA2 mutations was 50% in multiple case breast cancer families, and was 33% for the breast-ovarian cancer families. Our findings show that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Colombia. The spectrum of mutations differed completely to that previously reported in Hispanic families of predominantly Mexican origin from Southern California [1] suggesting that specific genetic risk assessment strategies for the different Hispanic populations in South America and in the United States need to be developed.
authors.affiliation: Division of Molecular Genome Analysis, German Cancer Research Center, Im Neuenheimer Feld 580, Heidelberg, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Torres
authors.forename: Muhammad Usman
authors.initials: MU
authors.lastname: Rashid
authors.forename: Fabian
authors.initials: F
authors.lastname: Gil
authors.forename: Angela
authors.initials: A
authors.lastname: Umana
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ramelli
authors.forename: Jose Fernando
authors.initials: JF
authors.lastname: Robledo
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tawil
authors.forename: Lilian
authors.initials: L
authors.lastname: Torregrosa
authors.forename: Ignacio
authors.initials: I
authors.lastname: Briceno
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D003105:Colombia / Q000208:ethnology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*