title: Genetic polymorphism of DNA base-excision repair genes (APE1, OGG1 and XRCC1) and their correlation with risk of lung cancer in a Chinese population.
abstract: OBJECTIVE
  Reactive oxygen species (ROS) and numerous carcinogens may cause DNA damage including oxidative base lesions that contribute to the risk of lung cancer. The base excision repair (BER) pathway could effectively remove oxidative lesions in which 8-oxoguanine glycosylase-1 (OGG1), x-ray repair cross-complementing 1 (XRCC1), and apurinic/apyimidinic endonuclease 1 (APE1) play key roles. The aim of this study was to analyze the polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of lung cancer.
  
  
  METHODS
  In a hospital-based, case-control study of 455 lung cancer cases and 443 cancer-free hospital controls, the SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their correlation with the risk of lung cancer in multivariate logistic regression models.
  
  
  RESULTS
  Individuals homozygous for the variants APE1 -141GG showed a protective effect for lung cancer overall (OR=0.62; 95% CI: 0.42-0.91; p=0.02) and for lung adenocarcinoma (OR=0.65; 95% CI, 0.44-0.96; p=0.03). When analyzing the combined effects of variant alleles, 84 patients and controls were identified who were homozygous for two or three of the potential protective alleles (i.e., OGG1 326Cys, XRCC1 399Gln and APE1 -141G). ORs were significantly reduced when all patients were analyzed (OR=0.62; 95% CI: 0.38-0.99; p=0.05).
  
  
  CONCLUSIONS
  The combined effects of polymorphisms within BER genes may contribute to the tumorigenesis of lung cancer.
authors: Department of Pathology, Third Military Medical University, Chongqing, China.
authors: Zheng
authors: Z
authors: Li
authors: Wei
authors: W
authors: Guan
authors: Meng-xia
authors: MX
authors: Li
authors: Zhao-yang
authors: ZY
authors: Zhong
authors: Cheng-yuan
authors: CY
authors: Qian
authors: Xue-qin
authors: XQ
authors: Yang
authors: Ling
authors: L
authors: Liao
authors: Zeng-peng
authors: ZP
authors: Li
authors: Dong
authors: D
authors: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D019943:Amino Acid Substitution; D044466:Asian People; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D012907:Smoking; 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