胃泌酸相关通路基因 GNAI3 中的新型 CpG-SNPs 与胃癌易感性的关系。

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

机构信息

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Biostatistics, School of Health, Nanjing Medical University, Nanjing, China.

出版信息

Gene. 2020 Apr 30;736:144447. doi: 10.1016/j.gene.2020.144447. Epub 2020 Feb 4.

DOI:10.1016/j.gene.2020.144447

PMID:32032744

Abstract

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). 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).

CONCLUSION

The CpG-SNP rs11810577 in GNAI3 in the gastric acid secretion pathway was significantly associated with susceptibility to gastric cancer.

摘要

背景

先前的研究表明，胃酸分泌与胃癌风险有关。然而，仍需要探讨相关通路的遗传变异是否会影响 GC 风险。

方法

对 1625 例胃癌病例和 2100 例对照进行了生物信息学研究，以探讨 11 个胃酸分泌途径基因中的遗传变异与胃癌风险的关系。我们使用逻辑回归模型，用比值比（ORs）和 95%置信区间（CIs）来估计 38 个单核苷酸多态性（SNPs）对胃癌易感性的影响。表达数量性状基因座（eQTL）分析和甲基化 eQTL（meQTL）分析用于计算基因表达的遗传效应。

结果

我们发现 GNAI3 中的 CpG-SNP rs11810577 与胃癌风险显著增加相关（OR=1.19，95%CI=1.07-1.32，P=1.12×10）。此外，rs11810577T 等位基因对胃组织中黏附分子与 Ig 样结构域 1（AMIGO1）的表达有负面影响，并增加了 AMIGO1 启动子区域 cg18220030 和 cg15694127 的甲基化水平。此外，我们发现 AMIGO1 在胃癌组织中的表达水平低于正常组织（P=0.037），与 TCGA 数据库的数据结果一致（P<1.0×10）。