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Biochemistry - Biophysics - Oncology - Public Health and Epidemiology - Respiratory Medicine

Cigarette Smoking and p16INK4a Gene Promoter Hypermethylation in Non-Small Cell Lung Carcinoma Patients: A Meta-Analysis
Published: Tuesday, December 13, 2011
Author: Bo Zhang et al.

by Bo Zhang, Wei Zhu, Ping Yang, Tao Liu, Mei Jiang, Zhi-Ni He, Shi-Xin Zhang, Wei-Qing Chen, Wen Chen


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 p16INK4a gene hypermethylation in lung cancer, but could not reach a unanimous conclusion.

Methods and Findings

Nineteen cross-sectional studies on the association between cigarette smoking and p16INK4a 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 p16INK4a 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 p16INK4a 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.


Cigarette smoking is positively correlated to p16INK4a gene hypermethylation in NSCLC patients.