Associations of RASSF1A, RAR, and CDH1 promoter hypermethylation with oral cancer risk: A PRISMA-compliant meta-analysis

Background:Oral tumor is a heterogeneous group of tumors, in which it has several different histopathological and molecular features. Recently, genetic and epigenetic alterations are often detected in the development of oral cancer. Gene promoter hypermethylation leads to the silencing of cancer related genes without changes of genes sequence. To clarify the effect of RAS association domain family protein 1a (RASSF1A), retinoic acid receptor beta (RAR), and E-cadherin (CDH1) promoter hypermethylation on the risk of oral cancer, we performed this meta-analysis.Methods:PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) databases were retrieved to identify eligible articles. Stata 12.0 software was used to analyze extracted data of the included articles. Odds ratios (ORs) with the corresponding 95% confidence interval (95% CI) were calculated to evaluate the associations of RASSF1A, RAR, and CDH1 promoter hypermethylation with oral cancer risk.Results:Around 23 literatures with 29 studies were included in the final meta-analysis, in which 12 studies were about RASSF1A promoter methylation, 4 studies were about RAR promoter methylation, and 13 studies were about CDH1 promoter methylation. Overall, the results of this meta-analysis showed that there were significant associations between RASSF1A, RAR, and CDH1 promoter hypermethylation and oral cancer risk (RASSF1A, OR=11.8, 95% CI=6.14-22.66; RAR, OR=20.35, 95% CI=5.64-73.39; CDH1, OR=13.46, 95% CI=5.31-34.17). In addition, we found that RASSF1A promoter hypermethylation exerted higher frequency in the tongue tumor than other site tumor in mouth (RASSF1A, tongue tumor vs other site tumor in mouth, unmethylation vs methylation, OR=0.65, 95%CI=0.44-0.98).Conclusion:RASSF1A, RAR, and CDH1 promoter hypermethylation might significantly increase the risk of oral cancer.