Alu Methylation and Risk of Cancer: A Meta-analysis

The association between Alu methylation and risk of cancer remains uncertain. This meta-analysis was conducted to elucidate this issue. PubMed and Web of Science up to December 31, 2018, and the reference lists of studies, as well as those presented in relevant meta-analyses and reviews were systematically searched. Standardized mean difference (SMD) in Alu methylation level between cases and controls were pooled using random effects model and assessed heterogeneity between strata by stratified factors using meta-regression model. Sensitivity analysis and publication bias test were also conducted. Twenty-five articles, including 2719 cases and 3018 controls were included in the meta-analysis. The significant difference in Alu methylation level between cancer cases and controls was greater in tissue (SMD = −1.89, 95% CI: −2.72, −1.05) than blood (SMD = −0.46, 95% CI: −0.82, −0.09), and heterogeneity was found in materials (P = 0.038). In tissue samples, Alu hypomethylation was found in carcinoma (SMD = −2.50, 95% CI: −3.51, −1.48), while not in non-carcinoma. The inverse associations were consistently found in subgroups stratified by data sources and quality score in tissue samples, and publication year was considered to be the potential source of between-study heterogeneity. Moreover, reduced Alu methylation level was found in the European subgroup, detection method of SIRPH and COBRA, and original data source in blood samples. Alu hypomethylation was associated with increased risk of cancer, which could be a potential biomarker for cancer.