ROLE OF HELICOBACTER PYLORI AND HOST GENE POLYMORPHISMS IN GASTRIC CARCINOGENESIS IN A KAZAKHS

Abstract

Emerging evidence indicated that common polymorphisms of TNF-α, IL1B, IL10, TP53, CD14, TLR4 genes might impact individual susceptibility to gastric cancer. Moreover, Helicobacter pylori plays an important role, provoking an increased susceptibility to the development of gastric pathologies. However, the results are still inconclusive, and specific alleles vary in different populations.  We conducted a study in the Kazakh population of the Northern region of Kazakhstan to identify potential risks or protective associations of SNP with gastric cancer, or H. pylori infection. We analyzed the association of SNPs in TNF-α (rs1800629 G/A), IL1B (rs16944 A/G), IL10 (rs1800872 G/T, rs1800871 G/A, rs1800896 A/C), TP53 (rs1042522 A/G), CD14 (rs2569190 G/A), and TLR4 (rs4986790 A/G, rs4986791 C/T) genes. We included cases with gastric cancer in a hospital-based Kazakh population (158 cases and 181 cancer-free controls). Identification of Helicobacter pylori was carried out by microbiological methods from biopsy specimens. Genotyping of the extended panel of polymorphisms of candidate genes was performed on the Quant Studio 12K Flex (Life Technologies). To estimate relative risk, odds ratio (OR) and 95% confidence interval (CI) were calculated, and P value 0.05 was considered statistically significant. We found that the polymorphisms of TP53 (rs1042522 A/G, OR: 2.32, 95% CI: 1.41-3.82, P-value=0.0009), CD14 (rs2569190 G/A, OR: 0.59, 95% CI: 0.36 - 0.96, P-value=0.035), and TLR4 (rs4986790 A/G, OR: 0.43, 95% CI: 0.19 - 0.95, P-value=0.038) are associated with gastric cancer risk. No significant association was observed between variant genotype polymorphisms of TNF-α, IL1B, IL10, TLR4 (ID: rs4986791) genes and gastric cancer risk. Further analyzes to assess the combined effect of TP53 rs1042522, CD14 rs2569190 and TLR4 rs4986791 and H. pylori infection on GC risk did not reveal significant associations. Our results testify to markers of GC risk among Kazakhs and may be the first step towards new approaches to diagnosis and prognosis in Kazakhstan.