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Aim. To study an association between Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene polymorphisms and breast cancer (BC) rate in women of the Kyrgyz population Material and Methods. Genomic DNA was obtainedfrom the whole blood of 117 breast cancer patients and 102 cancer-free healthy women residing in the Kyrgyz Republic. XRCC1 (Arg399Gln), TP53(Arg72Pro) and MDM2 (T309G) genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. Results. Women with the 399Gln allele had 1,57 fold higher risk (OR=1,57; p=0,034) of developing breast cancer than cases without these alleles. Individuals carrying the heterozygous genotype Arg399Gln had 2,77 fold higher risk (OR=2,77; p=0,0010) of BC. Notably, haplotype analyses revealed a stronger association with breast cancer risk if compare with data of the genotype analysis at each locus alone. The combination of heterozygous XRCC1 (Arg399Gln) variant and TP53 (Arg72Pro) genes increased even more the risk of BC (OR=3,98; p=0,0059). The combination of Arg399Gln and T309G genotypes of - XRCC1 and MDM2 genes is significant association with risk of BC (OR=3,0; p=0,034). We showed the combinations of Arg399Gln, Arg72Pro and T309Ggenotypes of-XRCC1, TP53 andMDM2 genes is related to the strong association with risk of BC in Kyrgyz women (OR=6,40; p=0,025). Conclusion. The polymorphisms Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene are associated with an increased risk of BC in Kyrgyz females. Combinations of unfavorable genotypes of several candidate genes increase even more the risk of BC.

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.

Цель - оценить ассоциацию генов TР53 (rs1042522) и XRCC1 (rs25487, rs1799782) со статусом по вирусу папилломы человека (ВПЧ) и уровнем онкомаркеров у женщин киргизской национальности с раком шейки матки (РШМ). Материалы и методы. Исследование проведено по типу «случай-контроль» и включало 103 женщин с гистологически верифицированным диагнозом РШМ и 102 женщин без онкологической патологии в анамнезе. Генотипирование пациентов осуществлялось методом ПЦР-ПДРФ. Проведено типировование ВПЧ 16 и 18 типов, в сыворотке крови определены уровни ракового эмбрионального антигена (РЭА) и SCC (squamous cell carcinoma antigen). Результаты. Генотипы Pro/Pro и Arg/Pro полиморфизма p.Arg72Pro гена ТР53 были ассоциированы с наличием у женщин с РШМ ВПЧ 16 типа - ОШ=1,98 (95% ДИ=1,01-3,86, p=0,04), а генотип Pro/Pro полиморфизма p.Arg72Pro гена ТР53 - с ВПЧ 18 типа - ОШ=9,15 (95% ДИ=1,78-46,96, p=0,002). Высокие уровни онкомаркеров РЭА и SCC чаще встречаются у пациентов с РШМ, имеющих размер первичного опухолевого узла более 4 см. Патологически высокие уровни РЭА и SCC ассоциированы преимущественно с ВПЧ 16 типа. Заключение. Наличие аллеля Pro (генотипов Pro/Pro и Pro/Arg) по ОНП p.Arg72Pro (ген ТР53) у женщин с РШМ ассоциировано с положительным статусом по высокоонкогенным ВПЧ 16 и 18 типов. Aim: Evaluation of the role of TР53 (rs1042522), XRCC1 (rs25487, rs1799782) gene depending on the human papillomavirus (HPV), morphological parameters of the tumor and tumor markers of the blood among women with cervical cancer (CC) in Kyrgyz Republic. Methods. This was a case-control study of 205 women of Kyrgyz origin with morphologically verified CC (N=103) and 102 women without cancer and chronic diseases. Genotyping was performed by PCR-RFLP method. HPV 16 and 18 types, levels of squamous cell carcinoma (SCC) and сarcinoembryonic antigen (CEA) tumor markers were detected. Results. A relationship has been identified between the genetic and clinical and biochemical parameters: Pro/Pro и Arg/Pro for single-nucleotide polymorphism p.Arg72Pro of the ТР53 gene were associated with HPV 16 type - OR 1,98 (95% CI=[1,01-3,86]), p=0,04; Pro/Pro for p.Arg72Pro of the ТР53 - with HPV 18 type - OR =9,15 (95% CI=[1,78-46,96]), p=0,002. Among patients with tumor size of more than 4 cm are more common high levels of CEA and SCC tumor markers. High levels of CEA and SCC are associated mainly with type 16 HPV. Conclusions. The results of the present study suggest that the presence of the Pro allele (genotypes Pro/Pro and Pro/Arg) by SNP p.Arg72Pro (TP53 gene) among women with cervical cancer is associated with a positive status for highly oncogenic HPV 16 and 18 types.