Helicobacter pylori Infection Synergizes with Three Inflammation-Related Genetic Variants in the GWASs to Increase Risk of Gastric Cancer in a Chinese Population

Abstract

BackgroundThree recent genome-wide association studies (GWASs) have reported that three SNPs (rs4072037, rs13361707 and rs2274223) located on genes related to host inflammatory response are significantly associated with susceptibility to gastric cancer (GC) in Chinese populations. Helicobacter pylori infection is also an important risk factor for GC through causing inflammatory response in the gastric mucosa. However, no study has established whether there are potential gene-environment interactions between these genetic variants and H. pylori infection to the risk of GC.MethodsWe genotyped three polymorphisms (rs4072037 at 1q22, rs13361707 at 5p13, and rs2274223 at 10q23) in 335 Chinese gastric adenocarcinoma patients and 334 controls. H. pylori serology was examined by enzyme-linked immunosorbent assay. Multivariable logistic regression models were used to evaluate the association between the variables and GC risk.ResultsWe confirmed that the three SNPs (rs4072037, rs13361707 and rs2274223) were significantly associated with GC susceptibility. H. pylori infection also significantly increased the risk of GC. Furthermore, there were joint effects between H. pylori infection and the three SNPs on the risk of GC. The most elevated risk of GC was found in subjects with H. pylori seropositivity and AA genotypes for rs4072037 [odds ratio (OR), 3.95; 95% confidence interval (CI), 2.29–6.79], H. pylori seropositivity and CT/CC genotypes for rs13361707 (OR, 2.68; 95% CI, 1.62–4.43), H. pylori seropositivity and AG/GG genotypes for rs2274223 (OR, 2.45; 95% CI, 1.55–3.88) compared with those with H. pylori seronegativity and other genotypes of each SNP. Significant interactions were observed between H. pylori seropositivity and the three SNPs (all P G× E <0.05) to the risk of GC.ConclusionThese findings indicate that the three SNPs (rs4072037, rs13361707 and rs2274223) identified in the GWASs may interact with H. pylori infection to increase the risk of GC.

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

“…On chromosome 5p13 all GC associated variants were in high LD ( r 2 > 0.8) to the most associated marker (rs6872282) and in high LD ( r 2 > 0.8) to all risk SNPs previously reported at this locus in Asians and Europeans . Thus, together with previous findings, our data provide evidence that one or more of these SNPs represent(s) the true GC conferring variant(s) in both the Asian and European population.…”

Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans

“…Previous studies have reported that the interaction between the genetic factors of a host and HP infection plays a significant role in gastric cancer carcinogenesis. The SNPs identified in previous studies were located on HP‐related genes ( IL‐1B, IL‐10, IL‐17, PGC, PTPN1, NOD1, NOD2 ), carcinogen detoxification‐related gene ( GSTP1 ), and cell proliferation‐related gene ( COX2 ) . In addition, DNA repair‐related genes, pattern‐recognition receptors, and genes identified in GWASs ( PSCA and MUC1 ) have important roles in gastric cancer carcinogenesis .…”

Gastrin and Gastric Cancer

“…Other risk factors that have been implicated include the following: cigarette smoking, H pylori infection, Epstein–Barr virus, radiation exposure, and prior gastric surgery for benign ulcer disease 18 . More recently, a number of investigators have shown that polymorphisms in inflammatory genes can be associated with gastric cancer risk 19, 20. Genetic risk factors include type A blood group, pernicious anemia, family history of gastric cancer, hereditary nonpolyposis colon cancer, and Li–Fraumeni syndrome 18 .…”