Novel CpG-SNPs in the gastric acid secretion pathway GNAI3 and susceptibility to gastric cancer.

BACKGROUND:Previous studies indicated that gastric acid secretion was associated with gastric cancer risk. However, it still needs to explore whether the related pathway genetic variation affects GC risk. METHODS:A bioinformatics study in 1625 gastric cancer cases and 2100 controls was conducted to investigate the relationship of genetic variants in eleven gastric acid secretion pathway genes and gastric cancer risk. We used logistic regression model with odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the effect of 38 single nucleotide polymorphisms (SNPs) on gastric cancer susceptibility. Expression quantitative trait loci (eQTL) analysis and the methylation eQTL (meQTL) analysis were used to calculate the genetic effect on gene expression. RESULTS:We identified that the CpG-SNP rs11810577 in GNAI3 was significantly increased gastric cancer risk (OR = 1.19, 95% CI = 1.07-1.32, P = 1.12 × 10^-3). Furthermore, rs11810577 T allele had a negative effect on adhesion molecule with Ig like domain 1 (AMIGO1) expression in gastric tissues and increased the methylation levels of cg18220030 and cg15694127 in the promoter region of AMIGO1. Moreover, we found AMIGO1 had a lower expression levels in gastric cancer tissues than normal tissues (P = 0.037), in agreement with the data results from The Cancer Genome Atlas (TCGA) database (P < 1.0 × 10^-4). CONCLUSION:The CpG-SNP rs11810577 in GNAI3 in the gastric acid secretion pathway was significantly associated with susceptibility to gastric cancer.

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