Associations Between RASSF1A Promoter Methylation and NSCLC: A Meta-analysis of Published Data

Background: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer(NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear,particularly in regarding links to clinicopathologic features.
Methods: Eligible studies were identified throughsearching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI)databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) werecalculated. Funnel plots were also performed to evaluate publication bias.
Results: Nineteen studies involving2,063 cases of NSCLC and 1,184 controls were included in this meta-analysis. A significant association wasobserved between RASSF1A methylation and NSCLC in the complete data set (OR = 19.42, 95% CI: 14.04-26.85, P < 0.001). Pooling the control tissue subgroups (heterogeneous/autologous) gave pooled ORs of 32.4(95% CI, 12.4-84.5) and 17.7 (95% CI, 12.5-25.0) respectively. Racial subgroup (Caucasian/Asian) analysisgave pooled ORs of 26.6 (95% CI, 10.9-64.9) and 20.9 (95% CI, 14.4-30.4) respectively. The OR for RASSF1Amethylation in poorly-differentiated vs. moderately/well-differentiated NSCLC tissues was 1.88 (95% CI, 1.32-2.68, P<0.001), whereas there were no significant differences in RASSF1A methylation in relation to gender,pathology, TNM stage and smoking behavior among NSCLC cases.
Conclusion: This meta-analysis suggests asignificant association between RASSF1A methylation and NSCLC, confirming the role of RASSF1A as a tumorsuppressor gene. Large-scale and well-designed case-control studies are needed to validate the associationsidentified in the present meta-analysis.