Association of RASSF1A promoter methylation with lung cancer risk: a meta-analysis

Abstract

RASSF1A, regarded as a candidate tumor suppressor, is frequently silenced and inactivated by methylation of its promoter region in many human tumors. However, the association between RASSF1A promoter methylation and lung cancer risk remains unclear. To provide a more reliable estimate we conducted a meta-analysis of cohort studies to evaluate the potential role of RASSF1A promoter methylation in lung carcinogenesis. Relevant studies were identified by searches of PubMed, Web of Science, ProQest and Medline databasesusing the following key words: 'lung cancer or lung neoplasm or lung carcinoma', 'RASSF1A methylation' or 'RASSF1A hypermethylation'. According to the selection standard, 15 articles were identified and analysised by STATA 12.0 software. Combined odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association between RASSF1A promoter methylation and lung cancer risk. A chi-square-based Q test and sensitivity analyses were performed to test between-study heterogeneity and the contributions of single studies to the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significant relationship between RASSF1A promoter methylation and lung cancer risk (OR, 16.12; 95%CI, 11.40-22.81; p<0.001) with no between-study heterogeneity. In subgroup analyses, increased risk of RASSF1A methylation in cases than controls was found for the NSCLC group (OR, 13.66, 95%CI, 9.529- 19.57) and in the SCLC group (OR, 314.85, 95%CI, 48.93-2026.2).