Department for Metabolism, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia.
Centre for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
Pathol Res Pract. 2020 May;216(5):152906. doi: 10.1016/j.prp.2020.152906. Epub 2020 Feb 28.
With the accumulation of evidence of the involvement of small-RNA-based regulatory mechanisms in carcinogenesis, genes encoding Ago proteins emerged as candidates for case-control studies on cancer. Since the data from association studies on various cancer types was not previously meta-analyzed, the potential effect of these variants on cancer risk in general was not previously evaluated. Therefore, we conducted a meta-analysis of all eligible studies, testing multiple genetic models of association. The identification of publication was based on PubMed database search, while OpenMeta-analyst, as well as MetaGenyo software, were used for quantitative data synthesis. AGO1 genetic variant rs636832 was found to associate with the overall cancer risk, assuming the overdominant genetic model (P = 0.030; OR = 0.865, 95%CI 0.759-0.986). For the same genetic variant, statistical significance was reached for the association with solid tumors, as well as with lung cancer susceptibility. Similar results were found in the Asians cohort for another AGO1 variant, rs595961. For rs4961280, none of the meta-analyses yielded statistically significant results. We conclude that genetic variants rs636832 and rs595961 located within AGO1 may represent susceptibility variants for specific types of cancer, while the association with malignant diseases was not determined for AGO2 variant rs4961280.
随着越来越多的证据表明基于小 RNA 的调节机制参与了癌症的发生，编码 Ago 蛋白的基因被认为是癌症病例对照研究的候选基因。由于以前没有对各种癌症类型的关联研究数据进行荟萃分析，因此这些变异体对癌症风险的潜在影响以前没有得到评估。因此，我们对所有合格的研究进行了荟萃分析，测试了多种关联的遗传模型。基于 PubMed 数据库搜索确定了文献的识别，而 OpenMeta-analyst 和 MetaGenyo 软件则用于定量数据综合。假设超显性遗传模型，发现 AGO1 基因变异 rs636832 与总体癌症风险相关（P=0.030；OR=0.865，95%CI 0.759-0.986）。对于相同的遗传变异，rs595961 与实体瘤和肺癌易感性的关联也具有统计学意义。在亚洲人群中，另一个 AGO1 变异 rs595961 也得到了类似的结果。对于 rs4961280，没有一项荟萃分析得出统计学意义的结果。我们的结论是，位于 AGO1 内的遗传变异 rs636832 和 rs595961 可能代表特定类型癌症的易感性变异，而 AGO2 变异 rs4961280 与恶性疾病的关联尚未确定。
