AOSOP7 Role of polymorphisms of DNA methyltransferases in risks of gastric cancer and atrophic gastritis

Abstract

Background DNA hypermethylation catalysed by DNA methyltransferases (DNMT) is thought to be involved in the development of gastric cancer. Single nucleotide polymorphisms (SNP) of DNMTs have been reported to be associated with susceptibility to various cancers. In this study, we investigated whether tag SNPs of DNMTs were associated with gastric cancer and, moreover, atrophic gastritis and Helicobacter pylori ( H. pylori ) infection, which are also risk factors for gastric cancer. Methods Twelve tagSNPs, rs2288349, rs2228611, rs2228612, rs16999593, and rs10420321 of DNMT1 , rs1550117 and rs13420827 of DNMT3a , and rs6119954, rs4911107, rs4911259, rs8008663, and rs1569686 of DNMT3b were genotyped by use of the TaqMan assay in 450 patients with non-cardiac gastric cancer and 1072 healthy controls. Serum antibodies to H. pylori and pepsinogen I and II were also tested using ELISA kits. Findings Three hundred and eleven (69.1%) patients with cancer and 562 (52.4%) controls were identified as being seropositive for H. pylori ( p DNMT3a was marginally associated with increased risk of gastric cancer compared with the GG genotype (OR 3.08, 95% confidence interval (CI) 1.00–9.61, p = 0.05). In terms of risk of atrophic gastritis, rs6119954 AA genotype of DNMT3b (OR 0.58, 95% CI 0.35–0.97) in H. pylori seropositive controls and rs1550117 AA genotype of DNMT3a (OR = 7.70, 95% CI 1.84–32.1) in seronegative controls were not significant. Moreover, three SNPs of DNMT1 , rs2288349 A allele, rs2228612 C allele, and rs10420321 G allele, and two haplotypes of DNMT1 , GATTA and AATCA, were associated with a higher risk of H. pylori infection in controls. Interpretation SNPs of DNMTs might be associated with risk of gastric cancer, atrophic gastritis, and H. pylori infection. However, further studies are needed to confirm this conclusion. Funding National Natural Science Fund of China (Grant No. 81072369 ). The authors declared no conflicts of interest.