Case Control Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2018; 24(5): 602-612
Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.602
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
Processing time: 82 Days and 16.8 Hours
Abstract
AIM

To investigate the interactions of the DNA repair gene excision repair cross complementing group 5 (ERCC5) and the metabolic gene glutathione S-transferase pi 1 (GSTP1) and their effects on atrophic gastritis (AG) and gastric cancer (GC) risk.

METHODS

Seven ERCC5 single nucleotide polymorphisms (SNPs) (rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassARRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population.

RESULTS

Two pairwise combinations (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk (Pinteraction = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions (ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility (Ptrend > 0.05). When the modification effect of Helicobacter pylori (H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions (ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status (Ptrend = 0.043).

CONCLUSION

There is a multifarious interaction between the DNA repair gene ERCC5 SNPs (rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.

Keywords: Excision repair cross complementing group 5, Glutathione S-transferase pi 1, Atrophic gastritis, Gastric cancer, Single nucleotide polymorphisms

Core tip: We detected seven excision repair cross complementing group 5 (ERCC5) single nucleotide polymorphisms (SNPs) and a glutathione S-transferase pi1 (GSTP1) SNP using the Sequenom MassARRAY platform in a Chinese population and used them to investigate their interactions and their effects on atrophic gastritis and gastric cancer risk. The results showed a multifarious interaction between the DNA repair gene ERCC5 SNPs (rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695. In addition, the cumulative effect of one pairwise interaction (ERCC5 rs873601-GSTP1 rs1695) was associated with an increased atrophic gastritis risk in the case of negative H. pylori status when the modification effect of H. pylori infection was evaluated.