Laboratory of Hygiene, Social & Preventive Medicine and Medical Statistics, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Greece.
Laboratory of Biochemistry, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece; Functional Proteomics and Systems Biology (FunPATh), Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, Thessaloniki, Greece; Genomics and Epigenomics Translational Research (GENeTres), Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, Thessaloniki, Greece.
Gene. 2019 Aug 20;710:333-340. doi: 10.1016/j.gene.2019.06.023. Epub 2019 Jun 13.
Gene promoter methylation is a common epigenetic event, taking place in the early phase of tumorigenesis, which has a great potential as a diagnostic and prognostic cancer biomarker. In this umbrella review, we provide an overview on the association between gene-promoter methylation of protein-coding genes and cancer risk based on currently available meta-analyses data on gene promoter methylation. We searched MEDLINE via PubMed and the Cochrane Database of Systematic Reviews for meta-analyses that examine the association between gene-promoter methylation and cancer, published until January 2019 in English. We used AMSTAR to assess the quality of the included studies and applied a set of pre-specified criteria to evaluate the magnitude of each association. We provide a comprehensive overview of 80 unique combinations between 22 different genes and 18 cancer outcomes, all of which indicated a positive association between promoter hypermethylation and cancer. In total, the 70 meta-analyses produced significant results under a random-effects model with odds ratios that ranged from 1.94 to 26.60, with the summary effect being in favor of the unmethylated group in all cases. Three of the strong evidence associations involve RASSF1 methylation on bladder cancer risk (OR = 18.46; 95% CI: 12.69-26.85; I = 0%), MGMT methylation on NSCLC (OR = 4.25; 95% CI: 2.83-6.38; I = 22.4%) and RARB methylation on prostate cancer (OR = 6.87; 95% CI: 4.68-10.08; I = 0%). Meta-analyses showed a moderate quality, AMSTAR score ranging from 4 to 9 (Mdn = 8; IQR: 7.0 to 8.0). As primary studies and meta-analyses on the subject accumulate, more genetic loci may be found to be highly associated with specific cancer types and hence the biomarker sets will become wider.
基因启动子甲基化是一种常见的表观遗传事件，发生在肿瘤发生的早期阶段，作为一种诊断和预后癌症的生物标志物具有很大的潜力。在这篇综述中，我们根据目前关于基因启动子甲基化的 meta 分析数据，提供了关于蛋白质编码基因基因启动子甲基化与癌症风险之间关联的概述。我们通过 MEDLINE 检索了 PubMed 和 Cochrane 系统评价数据库中的 meta 分析，这些 meta 分析研究了基因启动子甲基化与癌症之间的关系，截止到 2019 年 1 月，这些研究均以英文发表。我们使用 AMSTAR 评估了纳入研究的质量，并应用了一套预先设定的标准来评估每个关联的大小。我们提供了 80 个独特组合的综合概述，这些组合涉及 22 个不同基因和 18 个癌症结果，所有这些结果都表明启动子过度甲基化与癌症之间存在正相关。总的来说，70 项 meta 分析采用随机效应模型产生了显著的结果，优势比范围从 1.94 到 26.60，在所有情况下，汇总效应都有利于未甲基化组。三个具有强烈证据关联的研究涉及膀胱癌风险中 RASSF1 甲基化（OR=18.46；95%CI：12.69-26.85；I=0%）、非小细胞肺癌中 MGMT 甲基化（OR=4.25；95%CI：2.83-6.38；I=22.4%）和前列腺癌中 RARB 甲基化（OR=6.87；95%CI：4.68-10.08；I=0%）。Meta 分析的质量中等，AMSTAR 评分为 4 到 9（Mdn=8；IQR：7.0 到 8.0）。随着该主题的原始研究和 meta 分析的积累，可能会发现更多的遗传基因座与特定的癌症类型高度相关，因此生物标志物的范围将会更广。
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