Case Control Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2016; 22(12): 3372-3380
Published online Mar 28, 2016. doi: 10.3748/wjg.v22.i12.3372
Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan
Ching-Yu Lai, Ling-Ling Hsieh, Reiping Tang, Regina M Santella, Chung Rong Chang-Chieh, Chih-Ching Yeh
Ching-Yu Lai, Chih-Ching Yeh, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei 11031, Taiwan
Ling-Ling Hsieh, Department of Public Health, Chang Gung University, Taoyuan 333, Taiwan
Reiping Tang, Chung Rong Chang-Chieh, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Regina M Santella, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, United States
Chih-Ching Yeh, Department of Public Health, College of Public Health, China Medical University, Taichung 404, Taiwan
Author contributions: Lai CY, Hsieh LL, and Yeh CC designed the study, analyzed and interpreted the data, and drafted the manuscript; Tang R and Chang-Chieh CR enrolled participants; Santella RM conceived the study, participated in the experimental assays, and critically revised the manuscript; all authors have read and approved the final manuscript.
Supported by Chang Gung Memorial Hospital, No. CMRPD190071, No. CMRPD190072 and No. CMRPD190073; and NIEHS center, No. P30 ES009089.
Institutional review board statement: The study was approved by the ethics committee of Chang Gung Memorial Hospital (IRB permit number: 98-0573B).
Informed consent statement: All patients provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party directly or indirectly related to the study topic.
Data sharing statement: Technical appendix, statistical code, and data set are available with the corresponding author at ccyeh@tmu.edu.tw.
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: Chih-Ching Yeh, PhD, Professor, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan. ccyeh@tmu.edu.tw
Telephone: +886-2-27361661-6534 Fax: +886-2-27384831
Received: June 30, 2015
Peer-review started: July 4, 2015
First decision: October 15, 2015
Revised: November 8, 2015
Accepted: January 17, 2016
Article in press: January 18, 2016
Published online: March 28, 2016
Abstract

AIM: To evaluate the effects of OGG1 (Ser326Cys, 11657A/G, and Arg154His) and APE1 (Asp148Glu, and T-656G) polymorphisms on colorectal cancer (CRC) risk.

METHODS: We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and 736 age- and sex-matched healthy controls from a medical center in Taiwan. Genomic DNA isolated from the buffy coat was used for genotyping through polymerase chain reaction. Unconditional logistic regressions were used for calculating ORs and 95%CIs to determine the association between the genetic polymorphisms and CRC risk. Haplotype frequencies were estimated using PHASE software. Moreover, stratification analyses on the basis of sex, age at diagnosis, and tumor subsite and stage were performed.

RESULTS: The CRC risk was higher in patients with the OGG1 326Ser/Cys + Cys/Cys genotype (OR = 1.38, 95%CI: 1.03-1.85, P = 0.030), particularly high in patients with stage III + IV cancer (OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype. In addition, OGG1 11657G allele carriers had a 41% reduced CRC risk among stage 0-II patients (OR = 0.59, 95%CI: 0.35-0.98). The CRC risk was significantly higher among females with the APE1 Glu allele (OR = 1.41, 95%CI: 1.02-1.96). The APE1 148Glu/-656G haplotype was also associated with a significant CRC risk in females (OR = 1.36, 95%CI: 1.03-1.78).

CONCLUSION: OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of CRC in the Taiwanese population.

Keywords: APE1, OGG1, Taiwan, Colorectal cancer, Polymorphisms

Core tip: The associations between base excision repair DNA polymorphisms and colorectal cancer (CRC) risk is controversial. The present study examined the effects of OGG1 and APE1 polymorphisms on the CRC risk by using a large-scale sample of 727 CRC cases and 736 healthy controls. Results demonstrated that OGG1 326Cys and APE1 148Glu alleles were significantly associated with an increased CRC risk in patients with stage III + IV cancer (OR = 1.48) and females (OR = 1.41). Females carrying the APE1 148Glu/-656G haplotype also exhibited a 36% increased CRC risk. These findings suggest that OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of CRC.