Promoter Methylation of the Retinoic Acid Receptor Beta2 (RARβ2) Is Associated with Increased Risk of Breast Cancer: A PRISMA Compliant Meta-Analysis

Background Epigenetic studies demonstrate that an association may exist between methylation of the retinoic acid receptor beta2 (RAR beta 2) gene promoter and breast cancer onset risk, tumor stage, and histological grade, however the results of these studies are not consistent. Hence, we performed this meta-analysis to ascertain a more comprehensive and accurate association. Materials and Methods Relevant studies were retrieved from the PubMed, Embase and Chinese National Knowledge Infrastructure databases up to February 28, 2015. After two independent reviewers screened the studies and extracted the necessary data, meta-analysis was performed using Review Manager 5.2 software. Results Nineteen eligible articles, including 20 studies, were included in our analysis. Compared to non-cancerous controls, the frequency of RAR beta 2 methylation was 7.27 times higher in patients with breast cancer (odds ratio (OR) = 7.27, 95% confidence interval (CI) = 3.01-17.52). Compared to late-stage RAR beta 2 methylated patients, the pooled OR of early-stage ones was 0.81 (OR = 0.81, 95% CI = 0.55-1.17). The OR of low-grade RAR beta 2 methylated patients was 0.96 (OR = 0.96, 95% CI = 0.74-1.25) compared to high-grade RAR beta 2 methylated patients. Conclusion RAR beta 2 methylation is significantly increased in breast cancer samples when compared to non-cancerous controls. RAR beta 2 could serve as a potential epigenetic marker for breast cancer detection and management.