Does hypermethylation of CpG island in the promoter region of the E-cadherin gene increase the risk of lung cancer? A meta-analysis.

BACKGROUND: Hypermethylation of the CpG island in the promoter regions of tumor suppressor genes is common in the cancer tissue of non-small cell lung cancer (NSCLC) patients. Epithelial cadherin (E-cadherin) is a classic tumor suppressor gene of the cadherin superfamily and its promoter region is usually hypermethylated in malignant carcinomas. However, whether hypermethylation of the CpG island in the promoter region of E-cadherin increases the risk of lung cancer is unknown. We conducted a meta-analysis of E-cadherin gene promoter methylation status in cancer tissue (CT) and autologous controls (AC).

METHODS: Electronic databases were searched for E-cadherin gene promoter methylation and NSCLC. The hypermethylation status between CT and AC of NSCLC patients were compared and pooled by random or fixed effect models according to statistical heterogeneity across the included studies.

RESULTS: Eleven publications relevant to E-cadherin gene promoter hypermethylation and lung cancer risk were identified and included. E-cadherin gene promoter hypermethylation frequency in CT and AC was 0.32 (95% confidence interval [CI] 0.22-0.41) and 0.12 (95% CI 0.04-0.20), respectively, with statistical difference (P < 0.05). Significant statistical heterogeneity was found across the 11 studies (I2 = 54.5, P < 0.05). The data was pooled through a random effect model with an odds ratio of 4.21 (95% CI 2.33-7.58) in CT compared to AC.

CONCLUSION: The frequency of E-cadherin promoter hypermethylation in CT is significantly higher than in AC, indicating that promoter hypermethylation of E-cadherin plays an important role in NSCLC carcinogenesis.