Association between Cigarette Smoking and RASSF1A Gene Promoter Hypermethylation in Lung Cancer Patients: a Meta-analysis

  • Wu, Xiao-Ming (Laboratory of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology) ;
  • Chen, Yu (Laboratory of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology) ;
  • Shao, Yang (Laboratory of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology) ;
  • Zhou, Xiao-Long (Laboratory of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology) ;
  • Tang, Wen-Ru (Laboratory of Molecular Genetics of Aging and Tumor, Medical Faculty, Kunming University of Science and Technology)
  • Published : 2014.10.23


Objectives: Epidemiological studies have shown that molecular mechanisms underlying the development of lung cancers differ between smokers and unsmokers. Aberrant promoter methylation in some tumor suppressor genes is frequent in lung tumors from smokers but rare in those from non-smokers. Recently, many studies have investigated the association between cigarette smoking and RASSF1A gene promoter hypermethylation in lung cancer patients, but a unanimous conclusion could not be reached. We therefore performed this meta-analysis to derive a more precise estimation of any association. Study Design: An electronic search of PubMed and Chinese Biomedicine databases was conducted to select studies. A total of 19 case-control studies were chosen, and odds ratios (ORs) with confidence intervals (CIs) were used to assess the strength of associations. Results: The case-control studies covered 2, 287 lung cancer patients: 63.4%(1449) of the patients were smokers, 36.6% (838) were unsmokers. The overall results suggested that smokers with lung cancer had a 1.297-fold (95% CI: 1.066~1.580, p=0.010, p=0.087) higher risk for RASSF1A gene hypermethylation than the non-smokers. In the stratified analysis, an increased risk of RASSF1A gene hypermethylation in smokers than in non-smokers was found in Asian (OR=1.481, 95%CI: 1.179~1.861, p=0.001, p=0.186). Conclusions: This meta-analysis supports the idea that RASSF1A gene hypermethylation is associated with cigarette smoking-induced lung cancer.


Cigarette smoking;RASSF1A hypermethylation;meta-analysis;lung cancer


Supported by : National Nature Science Foundation of China, Nature Science Foundation of Yunnan Province


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