BRCA1 and BRCA2 mutations in breast and ovarian cancer families from south west Colombia

Abstract

Introduction: Breast cancer is the most common neoplasia of women from all over the world especially women from Colombia. 5%­10% of all cases are caused by hereditary factors, 25% of those cases have mutations in the BRCA1/BRCA2 genes. Objective: The purpose of this study was to identify the mutations associated with the risk of familial breast and/or ovarian cancer in a population of Colombian pacific. Methods: 58 high-risk breast and/or ovarian cancer families and 20 controls were screened for germline mutations in BRCA1 and BRCA2, by Single Strand Conformation Polymorphism (SSCP) and sequencing. Results: Four families (6.9%) were found to carry BRCA1 mutations and eight families (13.8%) had mutations in BRCA2. In BRCA1, we found three Variants of Uncertain Significance (VUS), of which we concluded, using in silico tools, that c.81­12C>G and c.3119G>A (p.Ser1040Asn) are probably deleterious, and c.3083G>A (p.Arg1028His) is probably neutral. In BRCA2, we found three variants of uncertain significance: two were previously described and one novel mutation. Using in silico analysis, we concluded that c.865A>G (p.Asn289Asp) and c.6427T>C (p.Ser2143Pro) are probably deleterious and c.125A>G (p.Tyr42Cys) is probably neutral. Only one of them has previously been reported in Colombia. We also identified 13 polymorphisms (4 in BRCA1 and 9 in BRCA2), two of them are associated with a moderate increase in breast cancer risk (BRCA2 c.1114A>C and c.8755­66T>C). Conclusion: According to our results, the Colombian pacific population presents diverse mutational spectrum for BRCA genes that differs from the findings in other regions in the country.

Identification of Variants (rs11571707, rs144848, and rs11571769) in the BRCA2 Gene Associated with Hereditary Breast Cancer in Indigenous Populations of the Brazilian Amazon

“…Similarly, the rs144848 had a significantly higher frequency in the Amazonian Amerindian peoples (50.78%) when compared to Americans (30.5%), Europeans (28.2%), South Asians (35.5%), East Asians (27.3%), and, particularly, Africans (12%). This variant has been pointed to act as a factor that confers a moderate risk for the development of BC [ 36 , 37 , 38 ]. Studies have already observed a relationship between the mutant homozygous genotype and the increased risk of breast cancer in women under 60 years of age [ 36 ] and family members of breast cancer patients [ 39 ].…”

“…Additionally, some small groups migrated from settled areas to uninhabited territories, giving rise to the first indigenous communities [ 36 ]. The genetic drift effect in these populations was even more driven by the small population size and inbreeding relationships, resulting in higher numbers of deleterious homozygous genotypes in the Native American populations [ 37 , 38 ].…”

Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients

“…In Colombia, previous reports described mutations in BRCA1/2 genes focused on hereditary/familial cases [ 17 , 21 , 26 , 27 ]. Even though, few studies analyzed mutation prevalence in BRCA1/ 2 genes from unselected BC patients, finding that their frequency ranges from 0.4 to 3.3% [ 20 , 21 ], which is concordant with our results, since the frequency of women with mutations in BRCA1/2 is 3.25%.…”

La lucha contra el cáncer de mama: una revisión sistemática sobre la prevalencia del BRCA en Colombia

“…La presencia de este gen tiene, además, un gran factor de agregación familiar, puesto que este se considera un gran factor de riesgo para la aparición de cáncer. La historia familiar supone ser uno de los indicativos más confiables a la hora de una posible incidencia de cáncer en torno a los parientes cercanos, como revelan varios estudios Cifuentes et al, 2019;Cortés et al, 2019;Vargas et al, 2019).…”

“…Sin embargo, considerando a Colombia como el país pluricultural y multidiverso que es, es necesaria una descripción completa de todas (o por lo menos, gran parte) de las regiones colombianas. Puesto que esta misma heterogeneidad impediría la creación de una estrategia común y aplicable a todos los contextos del país (Cifuentes et al, 2019). El componente genético, se recalca, es fundamental y no se puede obviar (Hernández et al, 2014).…”