The interleukin-6 (IL-6)/JAK/STAT3 signaling pathway plays a central role in inflammation-mediated cancers, including gastric cancer (GCa). We evaluated associations between 10 potentially functional single nucleotide polymorphisms (SNPs) of four essential genes in the pathway and GCa risk in a study of 1,125 GCa cases and 1,221 cancer-free controls. We found that a significant higher GCa risk was associated with IL-6 rs2069837G variant genotypes [adjusted odds ratios (OR) = 1.33; 95% confidence interval (CI) = 1.12-1.59 for AG + GG vs. AA)] and JAK1 rs2230587A variant genotypes (adjusted OR = 1.20; 95% CI = 1.02-1.43 for GA + AA vs. GG). We also found that a significant decreased GCa risk was associated with STAT3 rs1053004G variant genotypes (adjusted OR = 0.84; 95% CI = 0.71-0.99 for AG + GG vs. AA). The combined analysis of IL-6 rs2069837G and JAK1 rs2230587A variant risk genotypes revealed that individuals with one-or-two risk genotypes exhibited an increased risk for GCa (adjusted OR = 1.34; 95% CI = 1.13-1.59). Genotypes and mRNA expression correlation analysis using the data from the HapMap 3 database provided further support for the observed risk associations. Larger studies are warranted to validate these findings.
Keywords: gastric cancer; genetic susceptibility; genetic variate; interleukin-6/JAK/STAT3; signaling pathway.