Association between Cigarette Smoking and RASSF1A Gene Promoter Hypermethylation in Lung Cancer Patients: a Metaanalysis

Objectives: Epidemiological studies have shown that molecular mechanisms underlying the development oflung cancers differ between smokers and unsmokers. Aberrant promoter methylation in some tumor suppressorgenes is frequent in lung tumors from smokers but rare in those from non-smokers. Recently, many studies haveinvestigated the association between cigarette smoking and RASSF1A gene promoter hypermethylation in lungcancer patients, but a unanimous conclusion could not be reached. We therefore performed this meta-analysisto derive a more precise estimation of any association. Study Design: An electronic search of PubMed andChinese 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 thestratified analysis, an increased risk of RASSF1A gene hypermethylation in smokers than in non-smokers wasfound in Asian (OR=1.481, 95%CI: 1.179~1.861, p=0.001, p=0.186).
Conclusions: This meta-analysis supportsthe idea that RASSF1A gene hypermethylation is associated with cigarette smoking-induced lung cancer.