Abstract
PurposeThe main risk factor for familial breast cancer is the presence of mutations in BRCA1 and BRCA2 genes. The prevalence of mutations in these genes is heterogeneous and varies according to geographical origin of studied families. In Colombia mutations in these genes have been mainly studied on patients from Andean region. Bogotá and Medellin presented its own battery of mutations. This study aims to identify mutations in BRCA1–2 genes in women with familial breast cancer from different regions of Colombia.MethodsOne hundred four families with a history of breast cancer were sampled in different regions of Colombia, and the BRCA1 gene and exon 11 of the BRCA2 gene were sequenced. To predict the possible effects of sequence alterations found in protein function, different bioinformatics tools were used.ResultsA total of 33 variants were found; 18 in BRCA1 and 15 in BRCA2, of which 15 are unique variants of Colombia. In silico analysis established that alterations p.Thr790Ala, p.Arg959Lys and p.Glu1345Lys in the BRCA1 gene and variants p.Leu771Phe, p.Asn818Lys, p.Val859Ser*22 and p.Lys1032Ile in the BRCA2 gene are considered likely pathogenic. Both the mutations as the variants of unknown clinical significance, in their great majority, presented a specific region distribution and they were different from those reported in previous studies.ConclusionsIn this study we report the BRCA1 and BRCA2 spectrum of mutations and their distribution by regions in Colombia. Our results may help to design a diagnostic test including recurrent mutations for screening high risk to breast cancer families in Colombia.
Highlights
Breast cancer is the most common malignancy and the second leading cause of cancer death affecting women worldwide [1]
In silico analysis established that alterations p.Thr790Ala, p.Arg959Lys and p.Glu1345Lys in the BRCA1 gene and variants p.Leu771Phe, p.Asn818Lys, p.Val859Ser*22 and p.Lys1032Ile in the BRCA2 gene are considered likely pathogenic
When we analyzed the BRCA1 gene and exon 11 of BRCA2 gene of the 104 families by direct sequencing 33 sequence alterations were found, 18 in BRCA1 gene and 15 in BRCA2. Eighteen of these variants were polymorphic and shared with other populations in Latin America (11 in BRCA1 and 7 in BRCA2), and 15 sequence alterations are first reported in this study (7 in BRCA1 and 8 in BRCA2) (Table 2)
Summary
Breast cancer is the most common malignancy and the second leading cause of cancer death affecting women worldwide [1]. In Colombia, this disease is the secondmost frequently diagnosed malignancy, representing the leading cause of death in women according to statistics from the National Cancer Institute [2]. Breast cancer is a multifactorial disease that involves a complex combination of genetic and environmental factors. A positive family history of breast cancer increases the risk of developing this disease; this neoplasm is twice. In 1994 and 1995, the first genes associated with susceptibility to breast cancer, BRCA1 (OMIM # 113705) and BRCA2 (OMIM # 600185), were identified. A loss of function in BRCA1/2 genes results in an altered
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