Germline variants of BRCA1 and BRCA2 genes in population of Voronezh region of Russian Federation and their association with risk of breast cancer

In this study, we performed whole-gene analysis of BRCA1/2 in 145 breast cancer (BC) patients with family history of BRCA-associated cancers and 47 age-matched cancer-free control individuals with or without family history of cancer. Subjects for study were recruited in the Voronezh region of Russian Federation. We found that two polymorphic variants, rs1799967 (BRCA1) and rs4987117 (BRCA2), were strongly associated with the risk of BC. Both variants were not previously reported as associated with risk of breast cancer. Presence of rs4987117 variant increases risk of breast cancer onset (OR = 2.76, p-value = 0.022). Notably, although variant rs80357906 (5382InsC), reported as a risk factor for hereditary BC, was found more frequently in cancer patients than in cancer-free individuals (p = 0.192), no association with family history was observed. We also found 12 novel polymorphic variants in BRCA1/2 genes (2 in BRCA1 and 10 in BRCA2). However, none of these variants demonstrated association with the disease. Five germline variants were observed at high frequency (mean AF = 67.14%) and therefore can be considered as a common haplotype in Voronezh region of Russian Federation. In summary, our study demonstrates that known pathological variants of BRCA1/2 genes may not be reflective of breast cancer risk assessment when applied to the Russian population. Further, more extended population-specific studies are needed to reveal the reliable list of BRCA1/2 polymorphi...
Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - Category: Cytology Source Type: research