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.

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

“…Recently, Hernández et al [21] established the mutation frequency in the BRCA1/2 genes with Hispanel (115 Hispanic mutations panel), in patients with breast cancer not selected by family history from a region of Medellín. In total, 3 (1.2%) deleterious mutations were identified in 244 patients analyzed, of which 2 (67%) corresponded to mutations previously reported as founders in gene BRCA1 by Torres et al [12] (3450del4 in exon 11 and A1708E in exon 18). Rodríguez et al…”

“…Among these, BRCA1 3450del4 and BRCA2 6503delTT have also been reported, the first as a founder and the second as recurrent in the Colombian population, by Torres et al [12]. In a second study in the Chilean population performed by Gallardo et al [20], a group of 54 families with high risk of breast/ovarian cancer were evaluated (using SSCP, heteroduplex analysis, PTT, and sequencing analysis), The Oncologist ® identifying two mutations not previously reported: BRCA1 c.308_309insA and BRCA2 c.4970_4971insTG.…”

“…Of these, two corresponded to mutation 6633del5 reported in two nonrelated women. Recently, Felix et al [18] reported two new recurrent mutations in gene BRCA1 identified in 106 patients from the north of Brazil, mutation c.211A.G (p.R71G) followed by mutation 3450del4, which was previously reported as a founder in the Colombian population by Torres et al [12].…”

“…In the second population group (non-Ashkenazi) (57/134), 24 deleterious mutations were identified; 16 in BRCA1 and 8 in BRCA2, but none of them were identified in more than 1 nonrelated patient. However, among the nonrecurrent mutations identified in BRCA2, the 3034del4 mutation had been previously reported as founder in a Colombian population by Torres et al [12].…”

“…Torres et al [12] performed an analysis of mutations in the BRCA1/2 genes (using a range of techniques, including DHPLC, SSCP, and PTT, followed by direct DNA sequencing). They included 53 patients with breast cancer selected by family history and reported the identification of 3 founder mutations: 2 in BRCA1 (A1708E and 3450del4) and 1 in BRCA2 (3034del4).…”