The role of polymorphic variants of the <i>ERCC1</i> and <i>ERCC2</i> genes in the development of gastric cancer in the Kyrgyz population

Introduction. Gastric cancer is an aggressive malignant tumor of the gastrointestinal tract. Its onset and development are associated with genetic and external factors. Abnormalities in DNA repair genes, for example ERCC1 and ERCC2, can play a role in the development of this disease. Aim. To determine prognostic significance of ERCC1 (rs11615, rs3212986) and ERCC2 (rs13181) gene polymorphisms in the development of gastric cancer in the Kyrgyz population. Materials and methods. The study included 123 patients with malignant tumors of the stomach and 138 healthy individuals belonging to the Kyrgyz ethnic group. Genotyping was performed using allele-specific polymerase chain reaction. Statistical analysis included Fisher’s exact test and calculation of odds ratio (OR) for evaluation of associations between genotypes and clinical parameters. Genotyping results, histological and morphological tumor structures, patient age, tumor growth and location were compared using Fisher’s exact test. OR was determined through cross-tabulation. Results. Statistically significant association of CC genotype of the ERCC1 (rs3212986) polymorphic locus with patient age (41–50 and 61–70 years) was found. Genotypes TG and TT of the ERCC2 (rs13181) gene were associated with poorly differentiated adenocarcinoma. Additionally, it was shown that CA genotype and A allele of the rs3212986 (ERCC1) polymorphism can play a protective role decreasing the likelihood of gastric cancer development in the Kyrgyz population (OR 0.472; 95 % confidence interval 0.287–0.785 and OR 0.676; 95 % confidence interval 0.464–0.991 for CC genotype and allele A, respectively) (р = 0.046). Conclusion. Polymorphisms of the ERCC1 and ERCC2 genes can be associated with the risk of gastric cancer development in the Kyrgyz population. These data show the necessity of further studies investigating the role of these genes in gastric cancer and development of strategies for its prevention and treatment.