Association between genetic variants in genes encoding Argonaute proteins and cancer risk: A meta-analysis.

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_overdom = 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.

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