Interactions Of GWAS-identified Genetic Polymorphisms And Helicobacter Pylori Infection To The Risk Of Gastric Cancer

Backgroud&Aims: Three recent genome-wide association studies (GWASs) havereported some new single nucleotide polymorphisms (SNP) are associated withsusceptibility to gastric cancer (GC) in Chinese populations. There are three SNPs(rs4072037, rs13361707and rs2274223) located on genes related to hostinflammatory response. Helicobacter pylori infection is also an important risk factorfor GC through causing inflammatory response in the host epithelial tissues.Therefore, the present study was established to explore whether there are potentialgene–environment interactions between these SNPs and H. pylori infection to the riskof GC and further identify the high risk factors of GC.Methods:335gastric adenocarcinoma patients and334controls were recruited fromTongji hospital. We genotyped the three SNPs (rs4072037at1q22, rs13361707at5p13, and rs2274223at10q23) with Taqman probe method. H. pylori serology was examined by enzyme-linked immunosorbent assay (ELISA). Multivariable logisticregression models were used to evaluate the associations between the variables andGC risk and gene-environment interactions. Adjusted odds ratio (OR) and95%confidence interval (CI) were analyzed to show the relative risks. All data analysiswas performed with SPSS for Windows version17.0(SPSS Inc., Chicago, IL, USA).Results:We analyzed the associations between the three GWAS-identified SNPs(rs4072037, rs13361707and rs2274223) and risk of GC. Based on the dominantmodel, individuals with variant genotypes of the three SNPs were associated withaltered risks of GC after adjusting for sex, age, BMI, smoking and drinking status, andH. pylori serology (OR=0.50,95%CI:0.35–0.72for rs4072037; OR=1.63,95%CI:1.14–2.33for r13361707; and OR=1.33,95%CI:0.96–1.83for rs2274223). H.pylori infection also significantly increased the risk of GC (OR=1.74;95%CI:1.27-2.38). To further explore interactions between H. pylori infection and the threeSNPs on risk of GC, compared with those with H. pylori seronegativity and non-riskgenotypes, most elevated risks of GC were found in subjects with H. pyloriseropositivity and risk genotypes of the three SNPs. Compared with those with H.pylori seronegativity and AG/GG genotypes of rs4072037, subjects with H. pyloriseropositivity and AA genotypes were associated with the risk of GC (OR,3.96;95%CI,2.30-6.81). Compared with those with H. pylori seronegativity and TT genotypesof rs13361707, subjects with H. pylori seropositivity and CT/CC genotypes were associated with the risk of GC (OR,2.65;95%CI,1.60-4.37). Compared with thosewith H. pylori seronegativity and AA genotypes of rs2274223, subjects with H. pyloriseropositivity and AG/GG genotypes were associated with the risk of GC (OR,2.45;95%CI,1.55-3.87). Under the multiplicative interaction model, significantinteractions were observed between H. pylori seropositivity and the three SNPs (allPG×E<0.05) to the risk of GC.Conclusion:These findings indicate that the three SNPs (rs4072037, rs13361707andrs2274223) identified in the GWASs may interact with H. pylori infection to increasethe risk of GC. The three SNPs may play important roles in the process of H.pylori-related gastric carcinogenesis.