title: Cigarette smoking and p16INK4α gene promoter hypermethylation in non-small cell lung carcinoma patients: a meta-analysis.
abstract: BACKGROUND
  Aberrant methylation of promoter DNA and transcriptional repression of specific tumor suppressor genes play an important role in carcinogenesis. Recently, many studies have investigated the association between cigarette smoking and p16(INK4α) gene hypermethylation in lung cancer, but could not reach a unanimous conclusion.
  
  
  RESULTS
  Nineteen cross-sectional studies on the association between cigarette smoking and p16(INK4α) methylation in surgically resected tumor tissues from non-small cell lung carcinoma (NSCLC) patients were identified in PubMed database until June 2011. For each study, a 2×2 cross-table was extracted. In total, 2,037 smoker and 765 nonsmoker patients were pooled with a fixed-effects model weighting for the inverse of the variance. Overall, the frequency of p16(INK4α) hypermethylation was higher in NSCLC patients with smoking habits than that in non-smoking patients (OR = 2.25, 95% CI = 1.81-2.80). The positive association between cigarette smoking and p16(INK4α) hypermethylation was similar in adenocarcinoma and squamous-cell carcinoma. In the stratified analyses, the association was stronger in Asian patients and in the studies with larger sample sizes.
  
  
  CONCLUSIONS
  Cigarette smoking is positively correlated to p16(INK4α) gene hypermethylation in NSCLC patients.
authors.affiliation: Department of Toxicology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.forename: Zhi-Ni
authors.initials: ZN
authors.lastname: He
authors.forename: Shi-Xin
authors.initials: SX
authors.lastname: Zhang
authors.forename: Wei-Qing
authors.initials: WQ
authors.lastname: Chen
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D017594:Publication Bias; D018401:Sample Size; D012907:Smoking / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16