Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry

Abstract

BackgroundThere are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA.ResultsOf the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c.3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian.Materials and methodsThis study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry.ConclusionsThis is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families.

Genetics, tumor features and treatment response of breast cancer in Latinas

“…Most Latin American studies identified a higher rate of BRCA1 than BRCA2 mutations [37], however studies from Costa Rica [43], Cuba [50], Puerto Rico [51] and Uruguay [46] reported the opposite finding. However, prevalence information could be underestimated due to methodology procedures.…”

“…Several recent studies have evaluated BRCA mutation in Latin American countries, and some of them have documented prevalence studies in high-risk population and in unselected invasive BC cases in Mexico (six total studies, 6.3-23.0% in high risk, 4.3% in unselected) [34][35][36], Brazil (eight studies, 3.4-22.5%, 2.3%) [37][38], Argentina (two studies, 16.2-58.3%, unknown) [33,39], Colombia (five studies, 14.3-24.5%, 1.2-4.5%) [40][41], Chile (two studies, 7.1-20.4%, unknown) [42], Costa Rica (one study, 4.5%, unknown) [43], Cuba (one study, 2.6%, unknown) [44], Peru (one study, 4.9%, unknown) [45], Uruguay (one study, 17%, unknown) [46], Venezuela (one study,17.2%, unknown) [47], Trinidad and Tobago (one study, unknown, 10.4%) [48] and The Bahamas (one study, 27.1%, unknown) [49]. Most Latin American studies identified a higher rate of BRCA1 than BRCA2 mutations [37], however studies from Costa Rica [43], Cuba [50], Puerto Rico [51] and Uruguay [46] reported the opposite finding.…”

“…Two of these mutation (BRCA1 c.3331 3334delCAAG and BRCA1 c.5123C>A; along with BRCA2 c.5616 5620delAGTAA) was found in a screening of 244 unselected Colombian (Medellin) women with BC [56]. Three studies have evaluated more than 1000 Brazilians and describe recurrent BRCA mutations [37][38]57]. Esteves et al found BRCA1 ins6Kb (seven cases), c.5266dupC (four cases), 3261delGinsCC (three cases) in a total of 21 BRCA mutation in 612 medium and high risk for breast or ovarian cancer women [38].…”

“…Gomes et al found BRCA c.5266dupC (five cases) in a total of nine BRCA mutations from 402 BC women unselected for family background (9) [57]. Fernandes et al found BRCA1 c.5266dupC (18 cases), BRCA1 c.3331 3334delCAAG (eight cases) and BRCA2 c.2808 2811delACAA (three cases) in a total of 75 BRCA mutations from 349 high-risk breast and ovarian cancer cases [37]. Most ancestry proportion was European (70.6%), African (14.5%), NA (8.0%) and east Asian (6.8%), but no association was found between genetic ancestry and mutational status [37].…”

“…Fernandes et al found BRCA1 c.5266dupC (18 cases), BRCA1 c.3331 3334delCAAG (eight cases) and BRCA2 c.2808 2811delACAA (three cases) in a total of 75 BRCA mutations from 349 high-risk breast and ovarian cancer cases [37]. Most ancestry proportion was European (70.6%), African (14.5%), NA (8.0%) and east Asian (6.8%), but no association was found between genetic ancestry and mutational status [37]. Finally, results of Alemar et al suggest that the hypothesis of evaluating only recurrent BRCA mutations is not acceptable for some Latin American countries [58].…”