No abstract

100 thousand women (GLOBOCAN Cancer Fact Sheets: Cervical cancer). In developed countries, this cancer incidence shows the trend for reduction, which may associated with better awareness of risk factors, active prevention and advanced pre-cancer diseases recognition and treatment. On the contrary, in developing world, CC is the leading type of cancer among all malignant tumors in women. Some small, but persistent CC incidence increase is reported in Kyrgyzstan since mid-90s. In Kyrgyzstan, CC incidence in 2011 was 11.0 cases per 100,000, including 60.5% with stage I-II; 30.6% with stage III and 8.9% with stage IV. Mortality rate was 3.3 per 100,000, one-year mortality was 46.9%; and five-year survival was 39.7%. The mean age of CC patients was 40 years (Izmailova and Makimbetov, 2014). CC prevention is one of prioritized directions in public health and health promotion. CC is to large extent associated with human papilloma virus (HPV). HPV

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.

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.

Aim. Allele frequency and genotype distribution in the cervical cancer group were compared with those of the control group to determine whether polymorphism Arg72Pro of Р53 gene elevates the susceptibility of Kyrgyz women to cervical cancer (CC). Materials and Methods. A total of 102 women (mean age 53,5±10 years) of Kyrgyz nationality with cervical cancer were recruited into the study and 102 healthy women were used as the control group (mean age 46,5±8,5 years). The diagnosis of cervical cancer was confirmed histologically. 88 % (90/102) of women with cervical cancer were human papillomavirus (HPV) positive. 17 % (15/90) specimens were positive for HPV type 16, 48 % (43/90) were positive for HPV type 18 and 35 % (32/90) were positive both HPV - 16/18. Presence of human papillomavirus DNA types 16 and 18 was analyzed by polymerase chain reaction with hybridization-fluorescence detection. The Arg72Pro polymorphisms of the P53 gene were determined by the PCR-RFLP method. Results. No significant difference was found between genotype distributions in the cervical cancer patients and the control group (χ2=1,24; р=0,54). However, the Arg72Arg genotype and Arg72 allele was significantly more frequent in women with cervical cancers infected with HPV than in the control group (χ2=7,25; р=0,027 for для genotype, χ2=6,83; р=0,009 for allele). Women who are HIV positive and having the Arg72 allele had 1,94 fold (OR=1,94 [1,20-3,15]; р=0,009) higher risk of developing CC compared with subjects carrying neither of these alleles. HPV positive women carrying the genotype Arg72Arg had 1,85 fold (OR=1,85 [1,03-3,32]; р=0,027) higher risk of CC. Conclusion. The Arg72Arg genotype of р53 gene in HIV positive women from Kyrgyz Republic may represent a potential risk factor for the development of cervical cancer.