Abstract

We conducted a meta-analysis of cohort studies to evaluate the potential role of RASSF1A promoter methylation in colorectal carcinogenesis. A range of electronic databases were searched: PubMed (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM) (1982-2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with 95% confidence interval (95% CI) was calculated. Eleven clinical cohort studies with a total of 1,505 colorectal cancer (CRC) patients that met all inclusion criteria were included in our meta-analysis. The results of our meta-analysis revealed that the frequency of RASSF1A promoter methylation was strongly correlated with clinical stage (OR = 1.69, 95% CI 1.16-2.44, P = 0.006), histological grade (OR = 1.92, 95% CI 1.22-3.04, P = 0.005) and distant metastasis (OR = 2.59, 95% CI 1.46-4.60, P = 0.037) of CRC patients. However, we observed no positive correlations of RASSF1A promoter methylation with gender (OR = 1.04, 95% CI 0.74-1.46, P = 0.842), age (OR = 1.70, 95% CI 0.98-2.93, P = 0.057) and lymph node metastasis (OR = 1.65, 95% CI 0.87-3.14, P = 0.127) of CRC patients. Further subgroup analysis by ethnicity demonstrated that RASSF1A promoter methylation was correlated with clinicopathological characteristics of CRC patients among Asians (clinical stage: OR = 2.55, 95% CI 1.55-4.20, P < 0.001; histological grade: OR = 2.70, 95% CI 1.44-5.06, P = 0.002; lymph node metastasis: OR = 4.09, 95% CI 1.49-11.26, P = 0.006; distant metastasis: OR = 5.38, 95% CI 1.73-16.70, P = 0.004), but not among Caucasians and Africans (all P > 0.05). Our meta-analysis has shown positive correlations between aberrant promoter methylation of RASSF1A gene and clinicopathological characteristics of CRC patients, especially among Asians.

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