Copyright
©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Impact of SNP-SNP interactions of DNA repair gene ERCC5 and metabolic gene GSTP1 on gastric cancer/atrophic gastritis risk in a Chinese population
Liang Sang, Zhi Lv, Li-Ping Sun, Qian Xu, Yuan Yuan
Liang Sang, Department of Ultrasound, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Liang Sang, Zhi Lv, Li-Ping Sun, Qian Xu, Yuan Yuan, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Liang Sang, Zhi Lv, Li-Ping Sun, Qian Xu, Yuan Yuan, Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, Liaoning Province, China
Li-Ping Sun, Qian Xu, Yuan Yuan, National Clinical Research Center for Digestive Diseases, Xi’an 710032, Shaanxi Province, China
Author contributions: Yuan Y conceived and designed the experiments and revised the manuscript; Sang L, Sun LP, Xu Q and Lv Z performed the experiments; Sang L, Lv Z and Sun LP analyzed the data; Sang L wrote the paper.
Supported by the National Science and Technology Support Program, No. 2015BAI13B07.
Institutional review board statement: This study was approved by the Human Ethics Review Committee of China Medical University (Shenyang, China).
Informed consent statement: All participants provided written informed consent according to the Declaration of Helsinki and its later revision.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yuan Yuan, MD, Professor, Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Nanjing North Street, Shenyang 110001, Liaoning Province, China. yuanyuan@cmu.edu.cn
Telephone: +86-24-83282998 Fax: +86-24-83282998
Received: November 9, 2017
Peer-review started: November 9, 2017
First decision: November 21, 2017
Revised: December 5, 2017
Accepted: December 12, 2017
Article in press: December 12, 2017
Published online: February 7, 2018
ARTICLE HIGHLIGHTS
Research background
Previous studies suggested that the interactions between various inherited susceptibility genes may affect carcinogenesis in individuals. Single nucleotide polymorphisms (SNPs) are widely applied to the research of tumor incidence and prognostic evaluation.
Research motivation
We aimed to assess gene interactions amongst inherited polymorphisms between DNA repair gene excision repair cross complementing group 5 (ERCC5) SNPs and glutathione S-transferase pi1 (GSTP1) rs1695 to explore their possibility of predicting gastric cancer (GC) risk and identify combination biomarkers for precancerosis and GC.
Research objectives
The objective was to investigate the impact of interactions of the DNA repair gene ERCC5 with metabolic gene GSTP1 on atrophic gastritis (AG) and GC risk.
Research methods
Seven ERCC5 SNPs (rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 rs1695 SNP were detected using the Sequenom MassARRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population.
Research results
Two pairwise combinations (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk, and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect while ERCC5 rs873601-GSTP1 rs1695 shown a synergistic effect on AG risk. When the effect modification of Helicobacter pylori (H. pylori) infection was evaluated, the cumulative effect of one aforementioned pairs-way interaction (ERCC5 rs873601-GSTP1 rs1695) showed a risk in the case of negative status of H. pylori infection.
Research conclusions
DNA repair gene ERCC5 SNPs (rs2094258 and rs873601) and metabolic gene GSTP1 rs1695 polymorphism combinations were related to an increased or reduced AG risk. Moreover, the results also demonstrated a significant difference in the cumulative effect on AG risk in the H. pylori-negative subgroup.
Research perspectives
The interaction effects between genetic polymorphisms may be conductive to proposing further studies to discover gene-gene interactions between DNA repair genes and xenobiotic metabolic genes in gastric carcinogenesis.
