Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University, Hangzhou, China.
Ningbo Municipal Center for Disease Control and Prevention, Ningbo, China.
Am J Med Sci. 2020 May;359(5):271-280. doi: 10.1016/j.amjms.2020.03.002. Epub 2020 Mar 8.
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.
Alu 甲基化与癌症风险之间的关联尚不确定。本荟萃分析旨在阐明这一问题。
系统检索了 PubMed 和 Web of Science 数据库截至 2018 年 12 月 31 日的数据、研究参考文献列表，以及相关荟萃分析和综述中报告的数据。使用随机效应模型汇总病例组和对照组之间 Alu 甲基化水平的标准化均数差值（SMD），并使用分层因素的分层回归模型评估分层之间的异质性。还进行了敏感性分析和发表偏倚检验。
荟萃分析共纳入 25 篇文章，包括 2719 例病例和 3018 例对照。组织样本中癌症病例与对照组之间 Alu 甲基化水平的差异具有统计学意义（SMD=-1.89，95%CI：-2.72，-1.05），而血液样本中差异无统计学意义（SMD=-0.46，95%CI：-0.82，-0.09），且材料存在异质性（P=0.038）。在组织样本中，癌组织中 Alu 低甲基化（SMD=-2.50，95%CI：-3.51，-1.48），而非癌组织中 Alu 低甲基化。在组织样本中，根据数据来源和质量评分进行分层的亚组以及出版年份被认为是研究间异质性的潜在来源，均发现了一致的负相关。此外，在血液样本中，欧洲亚组、SIRPH 和 COBRA 检测方法以及原始数据源中发现了 Alu 甲基化水平降低。
Alu 低甲基化与癌症风险增加相关，可能是癌症的潜在生物标志物。
