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Systems approach to identify environmental exposures contributing to organ-specific carcinogenesis

机译:系统方法来识别导致器官特异性致癌作用的环境暴露

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Background: The most effective way to reduce cancer burden is Q2 prevention which is dependent on identifying individuals at risk for a particular cancer and counseling them to avoid exposure to causative agents. Other than a few well characterized environmental agents linked to specific cancers, linkage between any particular environmental exposure and a specific type of cancer is mostly unknown. Thus, we propose a systems approach to analyze publicly available large datasets to identify candidate agents that play a role in organ-specific carcinogenesis. Methods: Publicly available datasets for mRNA and miRNA expression in ovarian cancer were queried to define the differentially expressed genes that are also targets of differentially expressed miRNAs. These target genes were then used to query the Comparative Toxicogenomics Database to identify interacting chemicals and also were analyzed by Ingenuity Pathway Analysis to identify pathways. Results: The interacting chemicals interact with genes in known pathways in ovarian carcinogenesis and support the hypothesis that these chemicals are likely etiologic agents in ovarian carcinogenesis. Conclusion: A systems approach may prove useful to identify specific etiologic agents to better develop personalized preventive medicine strategies for those most at risk.
机译:背景:减轻癌症负担的最有效方法是预防Q2,这取决于确定有患特定癌症风险的个体并建议他们避免接触致病因素。除了与特定癌症相关的几种特征明确的环境因素外,大多数特定环境暴露与特定类型癌症之间的联系几乎是未知的。因此,我们提出了一种系统方法来分析可公开获得的大型数据集,以识别在器官特异性致癌作用中发挥作用的候选药物。方法:查询可用于卵巢癌的mRNA和miRNA表达的公开数据集,以定义差异表达基因,这些基因也是差异表达miRNA的靶标。然后将这些靶基因用于查询“比较毒物基因组学数据库”以鉴定相互作用的化学物质,并通过“独创性途径分析”进行分析以鉴定途径。结果:相互作用的化学物质与卵巢癌发生过程中已知途径的基因发生相互作用,并支持以下假设:这些化学物质可能是卵巢癌发生过程中的病因。结论:系统方法可能被证明对于识别特定病因的药物是有用的,以更好地为那些高危人群制定个性化的预防医学策略。

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