Prospective Study
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World J Gastroenterol. Jul 14, 2014; 20(26): 8700-8708
Published online Jul 14, 2014. doi: 10.3748/wjg.v20.i26.8700
APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans
Shi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang
Shi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China
Lin-Ang Wang, Chongqing Medical University, Chongqing 400016, China
Author contributions: Zhang SH and Wang LA contributed equally to this work; Zhang SH, Wang LA, Li Z, Peng Y, and Wang D designed the research; Zhang SH, Wang LA, Peng Y, Cheng Y, and Xiong YL performed the research; Zhang SH, Li Z, and Xiao H analyzed the data; Zhang SH and Wang LA wrote the paper; Cun YP, Dai N, and Wang D contributed to editing and revision of the manuscript.
Supported by Grants from the National Natural Science Foundation of China, No. 81171904 and No. 81001000
Correspondence to: Dong Wang, MD, PhD, Cancer Center, Daping Hospital and Research Institution of Surgery, Third Military Medical University, No. 10 Changjiang Zhi Rd, Yuzhong District, Chongqing 400042, China. dongwang64@hotmail.com
Telephone: +86-23-68757151 Fax: +86-23-68894062
Received: November 30, 2013
Revised: March 27, 2014
Accepted: April 21, 2014
Published online: July 14, 2014
Abstract

AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.

METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ2 tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.

RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m2 (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m2 (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).

CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.

Keywords: Apurinic endonuclease 1, Base excision repair, Single nucleotide polymorphisms, Colorectal cancer, X-ray repair cross-complementing groups

Core tip: There are discrepancies in reports concerning the association between polymorphisms in genes involved in the base excision DNA repair pathway (OGG1, APE1, and XRCC1) and colorectal cancer susceptibility. This study examines four of these polymorphisms in a Chinese Han population from the southwest region of China. Results show that the APE1 148 Glu/Glu genotype is associated with an increased risk of CRC. Moreover, analyses examining gene-behavior interactions revealed that smoking may influence the relationship between the XRCC1 Arg399Gln polymorphism and CRC risk.