Prevalence of BRCA1 and BRCA2 gene mutations in families with medium and high risk of breast and ovarian cancer in Brazil

Abstract

Of all malignant neoplasias affecting women, breast cancer has the highest incidence rate in Brazil. The objective of the present study was to determine the frequency of genetic modifications in families with medium and high risk for breast and ovarian cancer from different regions of Brazil. An exploratory, descriptive study was carried out on the prevalence of the BRCA1 and BRCA2 mutations in case series of high-risk families for breast and/or ovarian cancer. After heredogram construction, a blood sample was taken and DNA extraction was performed in all index cases. The protein truncation test was used to screen for truncated mutations in exon 11 of the BRCA1 gene and in exons 10 and 11 of the BRCA2 gene. Of the 612 individuals submitted to genetic testing, 21 (3.4%), 19 women and 2 men, had mutations in the BRCA1 or BRCA2 genes. Of the 19 BRCA1 mutations found in the 18 participants, 7 consisted of ins6kb mutations, 4 were 5382insC, 3 were 2156delGinsCC, 2 were 185delAG, 1 was C1201G, 1 was C3522T, and 1 was 3450del4. With respect to the BRCA2 gene, 3 mutations were found: 5878del10, 5036delA and 4232insA (one case each). The prevalence of germline mutations in the BRCA1 and BRCA2 genes found in the present study was lower than reported by other studies on high-risk Brazilian populations. The inclusion of individuals with medium risk may have contributed to the lower prevalence observed.

Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations

“…The HISPANEL is organized into 5 multiplex PCR reactions and detects 59 BRCA1 and 55 BRCA2 mutations, including 15 mutations already described in Brazilian patients [21][22][23][24][25][26]. Results of the HISPANEL analyses were compared to data from an independent cohort of 193 unrelated probands from the same Page 5 of 17 region who met the same inclusion criteria and had full BRCA testing by either Sanger or next generation sequencing at commercial diagnostic laboratories.…”

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

“…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].…”

“…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].…”

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

“…In Brazil, 6 studies that collectively screened 1151 individuals with hereditary BC reported 34 different BRCA mutations (24 in BRCA1 and 10 in BRCA2) [30][31][32][33][34][35], including 7 recurrent mutations (5 in BRCA1 and 2 in BRCA2) (Additional file 1: Table S1). In cohort B, a study by Carraro et al [36] (n = 54) detected another 5 mutations (2 in BRCA1 and 3 in BRCA2), including the recurrent mutation c.5266dupC (3.7%), which was also a recurrent mutation in hereditary BC (Additional file 1: Table S1).…”