title: Combined effects of cigarette smoking, gene polymorphisms and methylations of tumor suppressor genes on non small cell lung cancer: a hospital-based case-control study in China.
abstract: BACKGROUND
  Cigarette smoking is the most established risk factor, and genetic variants and/or gene promoter methylations are also considered to play an essential role in development of lung cancer, but the pathogenesis of lung cancer is still unclear.
  
  
  METHODS
  We collected the data of 150 cases and 150 age-matched and sex-matched controls on a Hospital-Based Case-Control Study in China. Face to face interviews were conducted using a standardized questionnaire. Gene polymorphism and methylation status were measured by RFLP-PCR and MSP, respectively. Logistic regressive model was used to estimate the odds ratios (OR) for different levels of exposure.
  
  
  RESULTS
  After adjusted age and other potential confounding factors, smoking was still main risk factor and significantly increased 3.70-fold greater risk of NSCLC as compared with nonsmokers, and the ORs across increasing levels of pack years were 1, 3.54, 3.65 and 7.76, which the general dose-response trend was confirmed. Our striking findings were that the risk increased 5.16, 8.28 and 4.10-fold, respectively, for NSCLC with promoter hypermethylation of the p16, DAPK or RAR beta gene in smokers with CYP1A1 variants, and the higher risk significantly increased in smokers with null GSTM1 and the OR was 17.84 for NSCLC with p16 promoter hypermethylation, 17.41 for DAPK, and 8.18 for RAR beta in smokers with null GSTM1 compared with controls (all p < 0.01).
  
  
  CONCLUSIONS
  Our study suggests the strong combined effects of cigarette smoke, CYP1A1 and GSTM1 Polymorphisms, hypermethylations of p16, DAPK and RAR beta promoters in NSCLC, implying complex pathogenesis of NSCLC should be given top priority in future research.
authors: Department of Environmental Medicine or Institute of Environmental Medicine, Zhejiang University School of Medicine, Zhejiang University, 310058 Hangzhou, China. jinedu@zju.edu.cn
authors: Yongtang
authors: Y
authors: Jin
authors: Heyun
authors: H
authors: Xu
authors: Chunye
authors: C
authors: Zhang
authors: Yunming
authors: Y
authors: Kong
authors: Yong
authors: Y
authors: Hou
authors: Yingchun
authors: Y
authors: Xu
authors: Shaoli
authors: S
authors: Xue
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D064550:Death-Associated Protein Kinases; D005260:Female; D016147:Genes, Tumor Suppressor; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D015996:Survival Rate
chemical_list: D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019363:Cytochrome P-450 CYP1A1; D004273:DNA, Neoplasm; D064550:Death-Associated Protein Kinases; D005982:Glutathione Transferase; D009363:Neoplasm Proteins; D018168:Receptors, Retinoic Acid; C000614131:CDKN2A protein, human; C082925:retinoic acid receptor beta