APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

• Published in: World journal of gastroenterology : WJG Vol. 20; no. 26; pp. 8700 - 8708
• Main Author: Zhang, Shi-Heng
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 14.07.2014
• Subjects: Adult; Aged; Aged, 80 and over; Alcohol Drinking - adverse effects; Alcohol Drinking - ethnology; Apurinic; Asian Continental Ancestry Group - genetics; Base; Body Mass Index; Case-Control Studies; Chi-Square Distribution; China - epidemiology; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - ethnology; Colorectal Neoplasms - genetics; DNA Glycosylases - genetics; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; DNA-Binding Proteins - genetics; endonuclease; excision; 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; Prospective Study; repair; Risk Factors; Singl; Smoking - adverse effects; Smoking - ethnology; X-ray Repair Cross Complementing Protein 1; Young Adult; X-ray repair cross-complementing groups; Apurinic endonuclease 1; Single nucleotide polymorphisms; Base excision repair; Colorectal cancer
• DOI: 10.3748/wjg.v20.i26.8700
• ISSN: 1007-9327; 2219-2840

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(OGG1Ser326Cys,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)].χ2tests 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<0.001relative 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 148Glu/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.