Potential of RASSF1A promoter methylation as biomarker for endometrial cancer: A systematic review and meta-analysis

Background An epigenetic approach to explaining endometrial carcinogenesis necessitates good understanding of Ras association domain family 1 isoform A (RASSF1A) promoter methylation data from primary studies. Aims Differential magnitude of reported associations between RASSF1A promoter methylation and endometrial cancer (EC) prompted a meta-analysis to obtain more precise estimates. Methods Literature search yielded eight included articles. We calculated pooled odds ratios (OR) and 95% confidence intervals and subgrouped the data by race. Sources of heterogeneity were investigated with outlier analysis. Results The pooled ORs indicated increased risk, mostly significant. The overall effect (OR 11.46) was reflected in the European outcome (OR 15.07). However, both findings were heterogeneous (I2 = 57‐70%) which when subjected to outlier treatment, erased heterogeneity (I2 = 0%) and retained significance (OR 9.85‐12.66). Significance of these pre- and post-outlier outcomes were pegged at P ≤ 0.0001. Only the Asian pre-outlier (OR 6.85) and heterogeneous (I2 = 82%) outcome was not significant (P = 0.12) but when subjected to outlier treatment, erased heterogeneity (I2 = 0%) and generated significance (OR 23.74, P ≤ 0.0001). Conclusions Consistent increased risk associations underpinned by significance and robustness render RASSF1A with good biomarker potential for EC.