INTERACTION BETWEEN POLYMORPHIC VARIANTS IN ТP53, XRCC1, TNFH, HMMR, MDM2,PALB2 GENES AND THEIR CONTRIBUTIONTO THE FORMATION OF A PREDISPOSITION TO BREAST CANCER IN WOMEN OF THE KYRGYZ POPULATION

Abstract

Aim: We studied the intergenic interactions and the contribution of polymorphic loci p.Arg72Pro (gene TP53), p.Gln399Arg (gene XRCC1), p.Arg194Trp (gene XRCC1), g.4682G>A (gene TNFa), p.Val353Ala (gene HMMR), p.14+309T>G (gene MDM2), g.38444T>G (gene PALB2) in the formation of predisposition to breast cancer (ВС) in women of Kyrgyz nationality. Material and method: The study included 103 women of the Kyrgyz ethnic group with the morphologically verified diagnosis of BC and 102 women without cancer and chronic diseases. Genotyping of single-nucleotide polymorphisms (SNPs) was performed using PCR-RFLP. Analysis of the intergenic interactions conducted with MDR 3.0.2 software. Results: Heterozygous genotype Gln/Arg of gene XRCC1 (ОR=3,15; 95% CI 1,78-5,58), the combination of Arg/Gln // Arg/Pro of genes XRCC1 (p.Gln399Arg) / TP53 (p.Arg72Pro) (OR=3,21; 95% CI 1,21-8,47), Arg/Gln // T/T of genes XRCC1 (p.Gln399Arg) / MDM2 (o.14+309T>G) (OR=3,18; 95% CI 0,99-10,7), Arg/Gln // G/G and Arg/Gln // G/A of genes XRCC1 (p.Gln399Arg) / TNFa (g.4682G>A) (OR=3,84; 95% CI 1,847,90) and (OR=3,91 95% CI 1,29-8,51 respectively), Arg/Gln // T/T of genes XRCC1 (p.Gln399Arg) / PALB2 (p.Thr1100=) (OR=2,92; 95% CI 1,59-5,37), as well as Arg/Gln // Arg/Arg and Arg/Gln // Arg/Trp for polymorphic loci p.Gln399Arg and p.Arg194Trp of gene XRCC1 (OR=2,48; 95% CI 1,12-5,19 and 0R=2,90, 95% CI 1,04-8,12 respectively) were associated with BC in Kyrgyz women. Conclusions: The results of the present study suggest that combinations of variants of ТP53, XRCC1, TNFa, HMMR, MDM2 и PALB2 genes may contribute to the genetic susceptibility of BC in Kyrgyz women.