The Role of Allelic Variants of Several Genes of Cytokines in the Development of Gastric Cancer

Abstract

Pro- and anti-inflammatory cytokines modulate the inflammatory response in the gastric mucosa. The analysis of associations of allelic variants of cytokine genes in the process of tumorous transformation of the gastric mucosa is an urgent problem. Its solution could make it possible to identify the features of production of inflammatory mediators by the immunocompetent cells during gastric carcinogenesis. The frequencies of alleles and genotypes of the rs1143634 and rs16944 loci of the IL1β gene, rs71941886 of the IL1RN gene, rs4073 of the IL8 gene, and rs1800872 of the IL10 gene were analyzed in 221 patients with established diagnosis of gastric cancer, as well as in 279 unrelated healthy individuals from the Republic of Bashkortostan. We discovered an association of the allele С and genotype C/C of the rs1143634 locus of the IL1β gene with a risk of development of malignant tumors of the stomach in men. We identified statistically significant differences in between patients and the control group in the distribution of frequencies of alleles and genotypes of the polymorphic variants: rs16944 of the IL1β gene and rs1800872 of the IL10 gene. Dependence of the associations with clinical features of the disease was also shown. Application of the APSampler algorithm revealed the combinations of alleles and genotypes associated with reduced and increased risk of the development of gastric cancer. The most significant were IL1β (rs1143634)*T + IL1β (rs16944)*T/T, IL8*A + IL10*A + IL1β (rs1143634)*T + IL1β (rs16944)*T, and IL10*A + IL1RN*2/2. The obtained results confirm the influence of the investigated allelic variants of cytokine genes on the risk of developing gastric cancer and play an important role in understanding the genetic structure of the studied pathology.