Association of RASSF1A Promoter Methylation with Lung Cancer Risk: a Meta-analysis

RASSF1A, regarded as a candidate tumor suppressor, is frequently silenced and inactivated by methylation ofits promoter region in many human tumors. However, the association between RASSF1A promoter methylationand lung cancer risk remains unclear. To provide a more reliable estimate we conducted a meta-analysis ofcohort studies to evaluate the potential role of RASSF1A promoter methylation in lung carcinogenesis. Relevantstudies were identified by searches of PubMed, Web of Science, ProQest and Medline databasesusing thefollowing key words: ‘lung cancer or lung neoplasm or lung carcinoma’, ‘RASSF1A methylation’ or ‘RASSF1Ahypermethylation’. According to the selection standard, 15 articles were identified and analysised by STATA12.0 software. Combined odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength ofthe association between RASSF1A promoter methylation and lung cancer risk. A chi-square-based Q test andsensitivity analyses were performed to test between-study heterogeneity and the contributions of single studiesto the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significantrelationship 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 incases 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).