APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans.

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)]. χ(2) 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/m(2) (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/m(2) (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.

• Authors: Shi-Heng Zhang, Lin-Ang Wang, Zheng Li, Yu Peng, Yan-Ping Cun, Nan Dai, Yi Cheng, He Xiao, Yan-Li Xiong, Dong Wang
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 26 Pg. 8700-8 (Jul 14 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 25024628 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• X-ray Repair Cross Complementing Protein 1
• XRCC1 protein, human
• DNA Glycosylases
• oxoguanine glycosylase 1, human
• APEX1 protein, human
• DNA-(Apurinic or Apyrimidinic Site) Lyase

Topics

• Adult
• Aged
• Aged, 80 and over
• Alcohol Drinking (adverse effects, ethnology)
• Asian People (genetics)
• Body Mass Index
• Case-Control Studies
• Chi-Square Distribution
• China (epidemiology)
• Colorectal Neoplasms (enzymology, ethnology, genetics)
• DNA Glycosylases (genetics)
• DNA-(Apurinic or Apyrimidinic Site) Lyase (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Gene-Environment Interaction
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Prospective Studies
• Risk Factors
• Smoking (adverse effects, ethnology)
• X-ray Repair Cross Complementing Protein 1
• Young Adult