Noel Pabalan1, Anthicha Kunjantarachot2, Chetana Ruangpratheep3, Hamdi Jarjanazi4, Denise Maria Christofolini5, Caio Parente Barbosa5, Bianca Bianco5. 1. Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand. Electronic address: npabalan@alumni.yorku.ca. 2. Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand. 3. Department of Pathology, Phramongkutklao College of Medicine, Bangkok, Thailand. 4. Environmental Monitoring and Reporting Branch, Ontario Ministry of the Environment and Climate Change, 125 Resources Road, Toronto, Ontario, Canada. 5. Human Reproduction and Genetics Center, Department of Collective Health, Faculdade de Medicina do ABC, Santo André/SP, Brazil.
Abstract
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.
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.