Targeted sequencing to discover germline variants in the BRCA1 and BRCA2 genes in a Russian population and their association with breast cancer risk

Sergei A. Solodskikh, Anna V. Panevina, Maria V. Gryaznova, Artem P. Gureev, Olga V. Serzhantova, Andrei A. Mikhailov, Alexander Y. Maslov, Vasily N. Popov

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

BRCA1 and BRCA2 are tumor suppressor genes involved in the repair of DNA damage and transcriptional regulation of the cell cycle. Alterations in BRCA1/2 lead to production of functionally defective proteins that impair DNA repair. Certain mutant variants of BRCA1/2 are strongly associated with increased risk of breast and ovarian cancers, with emerging data on association with other types of cancer. However, variability of BRCA1/2 in Russian populations remains understudied. In this study, we performed targeted sequencing of BRCA1/2 in 145 breast cancer (BC) patients with a family history of BRCA-associated cancers and 47 age-matched cancer-free control individuals with or without a family history of cancer. Subjects for this study were recruited in the Voronezh region of the Russian Federation. We found that two polymorphic variants, rs1799967 (BRCA1) and rs4987117 (BRCA2), were strongly associated with the risk of BC. Both variants have not been previously reported as associated with risk of breast cancer. Presence of the rs4987117 variant increases risk of breast cancer onset (OR = 2.76, p-value = 0.022). Notably, although variant rs80357906 (5382InsC) has been reported as a risk factor for hereditary BC, it was not significantly associated with breast cancer risk in our population (p = 0.192). 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 the Voronezh region of the 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 polymorphisms associated with risk of breast cancer in the Russian population.

Original languageEnglish (US)
Pages (from-to)51-57
Number of pages7
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume813
DOIs
StatePublished - Jan 2019

Keywords

  • BRCA1
  • BRCA2
  • Breast cancer
  • Cancer risk
  • Genetic polymorphism
  • Germline mutations
  • Next-generation sequencing
  • Polymorphic variant
  • Targeted sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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