title: APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Shi-Heng
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lin-Ang
authors.initials: LA
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.affiliation: 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.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Cun
authors.affiliation: 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.
authors.forename: Nan
authors.initials: N
authors.lastname: Dai
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects / Q000208:ethnology; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000208:ethnology; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: Apurinic endonuclease 1; Base excision repair; Colorectal cancer; Single nucleotide polymorphisms; X-ray repair cross-complementing groups