title: Contribution of the TP53, OGG1, CHRNA3, and HLA-DQA1 genes to the risk for lung squamous cell carcinoma.
abstract: BACKGROUND
  Recent genome-wide association studies (GWASs) have identified polymorphisms in several genes associated with lung cancer risk. Nevertheless, functional polymorphisms in DNA repair and metabolic genes that had been reported as being associated with risk for lung cancer, particularly for lung squamous cell carcinoma (SQC), were not examined in those studies. Therefore, significance of these functional polymorphisms was evaluated in a population, in which polymorphisms in the GWAS genes showed associations with lung SQC risk.
  
  
  METHODS
  Polymorphisms in three DNA repair genes, TP53, MDM2, and OGG1, and two metabolic genes, CYP1A1 and GSTM1, were examined for associations with lung SQC risk in a hospital-based case-control study consisting of 377 cases and 325 controls, which had been previously subjected to association studies on GWAS genes, CHRNA3, TERT, and HLA-DQA1.
  
  
  RESULTS
  Genotypes for two DNA repair genes, TP53 and OGG1, showed significant associations with SQC risk (p < 0.05), and those for two GWAS genes, CHRNA3 and HLA-DQA1, showed significant associations with SQC risk (P < 0.05) with odds ratios between 1.65 (95% confidence interval = 1.06-2.57 for OGG1) and 2.57 (95% confidence interval = 1.03-6.87 for CHRNA3). Marginally significant associations were also observed for MDM2 and CYP1A1 genes. Interactions among these polymorphisms on SQC risk were not observed.
  
  
  CONCLUSIONS
  Association of functional polymorphisms in DNA repair and metabolic genes with lung SQC risk was appreciated. This result indicates the necessity of reevaluation for the significance of functional polymorphisms in DNA repair and metabolic genes on lung cancer risk in other populations subjected to GWASs.
authors.affiliation: Biology Division, National Cancer Center Research Institute; †Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Mimaki
authors.forename: Kouya
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Aya
authors.initials: A
authors.lastname: Kuchiba
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000401:mortality; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D045647:DNA Glycosylases; D004273:DNA, Neoplasm; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D011978:Receptors, Nicotinic; D016159:Tumor Suppressor Protein p53; C069050:HLA-DQA1 antigen; C495901:TP53 protein, human; C479058:oxoguanine glycosylase 1, human