The role of low-penetrance alleles in predisposing the development of sporadic breast cancer

Abstract

Breast cancer (BC) is one of the most common oncological diseases in the world and has a complex polygenic multifactorial character. The simultaneous analysis of a large number of medium- and low-penetrance genes in the genesis of the sporadic forms of BC makes it possible to more accurately predict the individual risk of this disease, and the analysis of their intergenic associations will help to identify the most significant interactions between several of them. This would significantly simplify further screening studies. In this study, we analyzed all possible combinations of pathogenetically significant polymorphic variants for the key genes involved in (1) repair systems (XRCC1, XRCC3, and PALB2); (2) biotransformation of xenobiotics (NAT2, EPHX1, GSTP1, GSTT1, and GSTM1); (3) cell cycle control (HMMR, TP53); and (4) folate cycle (MTHFR) among patients from Belarus (eastern European region) with the sporadic forms of BC and in the control group. The combinations of genotypes (genetic profile) significantly modifying the risk of sporadic BC were identified using the multifactor dimensionality reduction (MDR). The genetic profile (combinations of genotypes) leading to a significant increase in the risk of sporadic BC is the presence of the G allele in SNP p.I105V (GSTP1), the T allele in SNP p.T241M (XRCC3), and the AA genotype in SNP p.E429A (MTHFR).