中國醫藥大學機構典藏 China Medical University Repository, Taiwan:Item 310903500/50522
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    Title: DNA甲基化、重金屬暴露與甲基化轉移酵素基因多形性和泌尿系統癌症之相關性研究(2/3)
    Authors: 鍾季容(Chi-Jung Chung);張兆祥(Chang,Chao-Hsiang)
    Contributors: 管理學院健康風險管理學系;中國附醫醫研部內科
    Keywords: 尿液重金屬;泌尿系統癌症;整體性DNA 甲基化;免疫組織染色;基因多 形性;heavy metals;urinary tract tumors;global DNA methylation;immunohistology;polymorphism
    Date: 2014-07-31
    Issue Date: 2013-10-17 11:20:14 (UTC+8)
    Abstract: 環境重金屬暴露來源,主要來自抽菸、食物、空氣、工廠作業環境等,其中抽菸 為泌尿系統癌症重要之危險因子之一,此外,中台灣地區工業區普遍,民眾是否經由 食物、空氣、工廠作業環境等暴露環境中重金屬,有待研究確認。過去文獻顯示環境 重金屬暴露與許多癌症發生有關,且細胞DNA 發生甲基化程度也與癌化有關。是否經 由重金屬暴露導致DNA 發生甲基化,進而與泌尿系統癌症發生有關,為本研究計畫亟 欲發展之重點方向。本研究計畫欲建立一病例對照研究法,第一年將建立中台灣民眾 罹患泌尿系統癌症以及相關健康對照組之基線尿液重金屬暴露含量(鉛、汞、鉻、鎳、 硒、鎘、砷、汞),以及利用問卷資料找尋可能的環境危險因子。第二年將建立週邊血 液以及泌尿系統癌症組織之DNA 甲基化程度測定,分析重金屬與細胞DNA 甲基化之 相關性。第三年將探討DNA 甲基轉移酵素基因多形性,包括DNMT1 Ile311Val、 Ala147Gly、His97Arg 和DNMT3A -448 A>G以及DNMT3B -283 T>C、-579 G>T和39179 G>T 之基因變異、DNA 甲基化程度與泌尿系統癌症之相關性。本研究擬利用內在劑量 與易感性生物標記進行尿液重金屬相關的泌尿系統癌症的分子流行病學研究。此外並 探討環境因子與環境因子及環境因子與基因對泌尿系統癌症的交互作用。
    Sources of environmental exposure to heavy metals are mainly from smoking, food, air, plant operating environment. Among these exposure routes, smoking is one of the important risk factors for urinary tract tumors. In addition, there are industrial areas in central Taiwan, and whether the residents is through food, air, plant operations and environmental exposure to heavy metals in the environment, to be studied to confirm. Previous literature shows that environmental heavy metal exposure is associated with the occurrence of many cancers. Cellular DNA methylation is also associated with the many kinds of cancers. Therefore, we will construct a case-control study to elucidate the relationships among the levels of heavy metals in human body, cellular DNA methylation and the gene polymorphisms of DNA methyltransferase enzyme as well as the risk of urinary tract tumors. For this study project, we will measure and establish the baseline urinary or blood levels of heavy metal content (lead, mercury, chromium, nickel, selenium, cadmium, arsenic and mercury) of the study participants in central Taiwan in the first year. Further, we will analyze the associated risk factors of environment and life styles for heavy metals exposure through the questionnaire. Next, we will construct the measurements of DNA methylation of peripheral blood and tissues of urinary tract tumors. Further, we will analyze the association between the levels of heavy metals and cellular DNA methylation in the second year. Finally, we will carry out the genotyping for the gene polymorphisms of DNA methyltransferase enzyme, including DNMT1 Ile311Val, Ala147Gly, His97Arg and DNMT3A -448 A> G and DNMT3B -283 T> C, -579 G> T and 39179 G> T. In addition, we will explore the relationships among the levels of DNA methylation, the gene polymorphisms and the risk of urinary tract tumors in the third year. Our study project intends to execute a molecular epidemiological study using the measurements of internal dose and biological markers of susceptibility to elucidate the mechanisms of heavy metals related urinary tract tumors carcinogenesis. We further to explore the interactions of the environment-environment factors and the environment- gene associations for the risk of urinary system cancers.
    Appears in Collections:[Department of Health Risk Management] Research reports

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