Polymorphisms in Gstm1, Gstp1 and Gstt1 Genes and Breast Cancer Risk in Women From Kyrgyzstan

Abstract

Aim: We studied the intergenic interactions and the contribution of polymorphic loci for GSTT1, GSTM1, GSTP1 genes in the formation of predisposition to breast cancer (ВС) in women of Kyrgyz nationality. Material and method: The study included 87 women of the Kyrgyz ethnic group with the morphologically verified diagnosis of BC and 96 women without cancer and chronic diseases. Genotyping of single-nucleotide polymorphisms (SNPs) was performed using PCR-RFLP for rs1695 GSTP1 gene. Deletion polymophisms in GSTT1 and GSTM1 genes were determined using allele-specific real-time PCR. Analysis of the intergenic interactions conducted with MDR 3.0.2 software. Results: Among women of Kyrgyz nationality, deletion of the GSTM1 gene region is a genetic marker associated with an increased likelihood of developing breast cancer (OR = 2.18, 95% CI 1.38-3.44), p = 0.0007). The absence of deletion in this gene is associated with a protective effect. Analysis of polymorphic markers (GSTT1 gene) and p.Ile105Val (GSTP1 gene) did not reveal statistically significant differences in the frequency distribution of genotypes and alleles between breast cancer patients and women from the comparison group (p > 0.05). Analysis of intergenic interactions using MDR analysis showed that, with the simultaneous presence of the Arg/Gln genotypes (XRCC1 gene) and (GSTM1 gene), the probability of developing breast cancer was - OR = 2.63. Conclusions: Deletion of the GSTM1 gene and combinations of the Arg/Gln genotypes (XRCC1 gene) and (GSTM1 gene) may contribute to the genetic susceptibility of BC in Kyrgyz women.