Impact of SNP-SNP interactions of DNA repair gene ERCC5 and metabolic gene GSTP1 on gastric cancer/atrophic gastritis risk in a Chinese population

doi:10.3748/wjg.v24.i5.602

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World Journal of Gastroenterology

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1007-9327

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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.

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

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.