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.
Gene. 2021 Jan 15;766:145132. doi: 10.1016/j.gene.2020.145132. Epub 2020 Sep 8.
Dysfunctions in mechanisms of gene regulation based on RNA interference are recognized as a common feature of the molecular basis of cancer pathogenesis. Therefore, as one of the crucial components of the machinery involved in the biogenesis of both siRNAs and microRNA molecules, DICER was recognized as one of the candidates for the research in the field of carcinogenesis. Due to their potential functional properties, several genetic variants located within DICER1 gene were analyzed for their possible association with the susceptibility to cancer through case-control studies. In order to elucidate their effect on the overall cancer risk, we conducted an updated meta-analysis of all eligible association studies. The publications were selected based on PubMed database search, while OpenMeta-analyst and MetaGenyo software were used for quantitative data synthesis. Statistically significant results were found for the association of rs1057035 with the overall cancer risk under multiple genetic models (P < 0.001, OR = 0.870, 95% CI = 0.812-0.933; P = 0.009, OR = 0.896, 95% CI = 0.825-0.973; P < 0.001, OR = 0.874, 95% CI = 0.817-0.934; P = 0.004, OR = 0.858, 95% CI = 0.773-0.953). Other selected genetic variants within DICER1, rs13078, rs1209904 and rs3742330, did not show the association with the overall susceptibility to malignant diseases. We conclude that rs1057035 may represent a potential biomarker associated with the risk of developing cancer, which requires a confirmation in a larger set of studies.
基于 RNA 干扰的基因调控机制障碍被认为是癌症发病机制分子基础的共同特征。因此，作为 siRNA 和 microRNA 分子生物发生所涉及的机制的关键组成部分之一，DICER 被认为是致癌研究领域的候选者之一。由于其潜在的功能特性，对 DICER1 基因内的几个遗传变异进行了分析，以研究它们与癌症易感性的可能关联，通过病例对照研究。为了阐明它们对整体癌症风险的影响，我们对所有合格的关联研究进行了更新的荟萃分析。根据 PubMed 数据库搜索选择出版物，而 OpenMeta-analyst 和 MetaGenyo 软件用于定量数据综合。在多种遗传模型下，rs1057035 与总体癌症风险的关联存在统计学意义（P < 0.001，OR = 0.870，95%CI = 0.812-0.933；P = 0.009，OR = 0.896，95%CI = 0.825-0.973；P < 0.001，OR = 0.874，95%CI = 0.817-0.934；P = 0.004，OR = 0.858，95%CI = 0.773-0.953）。DICER1 内其他选定的遗传变异，rs13078、rs1209904 和 rs3742330，与总体恶性疾病易感性无关。我们得出结论，rs1057035 可能代表与癌症发病风险相关的潜在生物标志物，这需要在更大的研究集中进行验证。
