Impact of interaction between interleukin-6 gene polymorphism and Helicobacter pylori infection on susceptibility to gastric cancer

Abstract

Objective This study aimed to evaluate the association between four single nucleotide polymorphisms (SNPs) of the interleukin-6 (IL-6) gene and gastric cancer (GC), and impact of interaction between IL-6 SNPs and Helicobacter pylori (H. pylori) infection on susceptibility to GC. Methods Logistic regression was used to test the relationships between four SNPs of IL-6 gene and GC susceptibility. A generalized multifactor dimensionality reduction (GMDR) model was employed to assess the interaction effect between IL-6 gene and H. pylori infection on GC risk. Results Logistic regression analysis indicated that the rs1800795-C allele was associated with increased GC risk, adjusted ORs (95% CI) were 1.80 (1.21–2.41) (CC vs. GG) and 1.68 (1.09–2.30) (C vs. G), respectively. The rs10499563-C allele was associated with decreased risk of GC, and adjusted ORs (95% CI) were 0.62 (0.31–0.93) (TC vs. TT), 0.52 (0.18–0.89) (CC vs. TT) and 0.60 (0.29–0.92) (C vs. T), respectively. GMDR methods found a two-dimensional model combination (including rs1800795 and H. pylori infection) was statistically significant. The selected model had testing balanced accuracy of 59.85% and the best cross-validation consistencies of 10/10 (P = 0.0107). Compared with H. pylori-negative subjects with rs1800795- GG genotype, H. pylori-positive participants with GC or CC genotype had the highest risk of GC, the OR (95% CI) was 3.34 (1.78–4.97). Conclusion The rs1800795-C allele was associated with increased GC risk and the rs10499563-C allele was associated with decreased GC risk. The interaction between rs1800795 and H. pylori infection was also correlated with increased risk of GC.