title: Association of DNA base-excision repair XRCC1, OGG1 and APE1 gene polymorphisms with nasopharyngeal carcinoma susceptibility in a Chinese population.
abstract: BACKGROUND
  Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles.
  
  
  OBJECTIVE
  To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma.
  
  
  METHODS
  We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models.
  
  
  RESULTS
  After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02- 3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1- 141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants ,was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004).
  
  
  CONCLUSIONS
  This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1- 141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China E-mail : dongwang64@hotmail.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.forename: Shi-Heng
authors.initials: SH
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics*; D002277:Carcinoma / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012907:Smoking / Q000009:adverse effects; D000076105:X-ray Repair Cross Complementing Protein 1
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