Meta-Analysis
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 5081-5089
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.5081
Relationship between apurinic endonuclease 1 Asp148Glu polymorphism and gastrointestinal cancer risk: An updated meta-analysis
Zhi-Jun Dai, Yong-Ping Shao, Hua-Feng Kang, Wei Tang, Dan Xu, Yang Zhao, Di Liu, Meng Wang, Peng-Tao Yang, Xi-Jing Wang
Zhi-Jun Dai, Hua-Feng Kang, Yang Zhao, Di Liu, Meng Wang, Peng-Tao Yang, Xi-Jing Wang, Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Zhi-Jun Dai, Yong-Ping Shao, Dan Xu, Center for Translational Medicine, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an 710049, Shaanxi Province, China
Wei Tang, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710061, Shaanxi Province, China
Author contributions: Dai ZJ, Shao YP and Kang HF contributed equally to this work; Dai ZJ, Kang HF and Wang XJ designed the research; Shao YP, Xu D, Zhao Y, Liu D and Yang PT performed the research; Tang W, Wang M and Wang XJ analyzed the data; Dai ZJ and Shao YP wrote the paper.
Supported by National Natural Science Foundation of China, No. 81471670 and No. 81102711; the International Cooperative Project of Shaanxi Province, China, No. 2013KW-32-01; and the Fundamental Research Funds for the Central Universities, China and Specialized Research Fund of the Second Affiliated Hospital of Xi'an Jiaotong University, China, No. RC (GG) 201203.
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: Zhi-Jun Dai, MD, PhD, Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, No. 157, West 5th Road, Xi’an 710004, Shaanxi Province, China. dzj0911@126.com
Telephone: +86-29-87679226 Fax: +86-29-87679282
Received: August 21, 2014
Peer-review started: August 21, 2014
First decision: September 27 ,2014
Revised: October 28, 2014
Accepted: December 5, 2014
Article in press: December 8, 2014
Published online: April 28, 2015
Abstract

AIM: To evaluate the relationship between apurinic endonuclease 1 (APE1) Asp148Glu polymorphism and the susceptibility to gastrointestinal (GI) cancers.

METHODS: We searched PubMed, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure (CNKI) databases updated on July 15, 2014 for relevant studies. Only case-control studies comparing APE1 Asp148Glu polymorphism and GI cancer risk were included. We excluded studies reporting only standardized incidence ratios without control groups and those without detailed genotyping data. Meta-analysis was performed on 17 studies involving 4856 cancer patients and 6136 cancer-free controls. Review Manager version 5.1 was used to perform the meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated under the allele contrast, homozygous, heterozygous, dominant and recessive genetic models. We also conducted subgroup analyses stratified by ethnicity and cancer type. Publication bias was evaluated using Begg’s test.

RESULTS: The meta-analysis showed a significant association between APE1 Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall population (G vs T: OR = 1.18; 95%CI: 1.05-1.32; TG vs TT: OR = 1.28; 95%CI: 1.08-1.52; TG + GG vs TT: OR = 1.32; 95%CI: 1.10-1.57). Stratified analysis by ethnicity revealed a statistically increased GI cancer risk in Asians (G vs T: OR = 1.27; 95%CI: 1.07-1.51; GG vs TT: OR = 1.58; 95%CI: 1.05-2.38; TG vs TT: OR = 1.30; 95%CI, 1.01- 1.67; and TG + GG vs TT: OR = 1.38; 95%CI: 1.07-1.78), but not in Caucasians. Further subgroup analysis by cancer type indicated that APE1 Asp148Glu polymorphism may contribute to gastric cancer risk. However, Asp148Glu has no significant association with colorectal or esophageal cancer risk in any genetic model.

CONCLUSION: This meta-analysis suggests that the APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk, especially in gastric cancer.

Keywords: Apurinic endonuclease 1, Single nucleotide polymorphism, Gastrointestinal cancers, Cancer risk, Meta-analysis

Core tip: Apurinic endonuclease 1 (APE1) plays an important role in the DNA repair system and therefore has been implicated in human carcinogenesis. Many studies have suggested an association between the APE1 Asp148Glu polymorphism and gastrointestinal cancer susceptibility. However, the results remained inconclusive. We performed a meta-analysis on pooled data from previously published studies. The results showed that the APE1 Asp148Glu polymorphism G allele is associated with an increased gastrointestinal cancer risk, especially in gastric cancer.