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Cigarette Smoking and p16INK4α Gene Promoter Hypermethylation in Non-Small Cell Lung Carcinoma Patients: A Meta-Analysis

Author

Listed:
  • Bo Zhang
  • Wei Zhu
  • Ping Yang
  • Tao Liu
  • Mei Jiang
  • Zhi-Ni He
  • Shi-Xin Zhang
  • Wei-Qing Chen
  • Wen Chen

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 p16INK4α 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 p16INK4α 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 p16INK4α 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 p16INK4α 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. Conclusion: Cigarette smoking is positively correlated to p16INK4α gene hypermethylation in NSCLC patients.

Suggested Citation

  • Bo Zhang & Wei Zhu & Ping Yang & Tao Liu & Mei Jiang & Zhi-Ni He & Shi-Xin Zhang & Wei-Qing Chen & Wen Chen, 2011. "Cigarette Smoking and p16INK4α Gene Promoter Hypermethylation in Non-Small Cell Lung Carcinoma Patients: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 6(12), pages 1-9, December.
    • Handle: RePEc:plo:pone00:0028882
    DOI: 10.1371/journal.pone.0028882
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    References listed on IDEAS

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    1. Ina Rhee & Kam-Wing Jair & Ray-Whay Chiu Yen & Christoph Lengauer & James G. Herman & Kenneth W. Kinzler & Bert Vogelstein & Stephen B. Baylin & Kornel E. Schuebel, 2000. "CpG methylation is maintained in human cancer cells lacking DNMT1," Nature, Nature, vol. 404(6781), pages 1003-1007, April.
    2. Gerda Egger & Gangning Liang & Ana Aparicio & Peter A. Jones, 2004. "Epigenetics in human disease and prospects for epigenetic therapy," Nature, Nature, vol. 429(6990), pages 457-463, May.
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    Cited by:

    1. Zhang Lou-Qian & Yin Rong & Li Ming & Yang Xin & Jiang Feng & Xu Lin, 2013. "The Prognostic Value of Epigenetic Silencing of p16 Gene in NSCLC Patients: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-7, January.

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