台灣西南部地區長期飲用含砷井水居民其砷代謝相關基因多形性與皮膚癌之相關性研究

Genetic polymorphisms associated with arsenic methylation and skin cancer risk in southwestern Taiwan

陳郁屏(Yu-Ping Chen)

指導教授 ： 陳建仁 ； 王根樹

國立臺灣大學/公共衛生學院/環境衛生研究所/碩士(2006年)

https://doi.org/10.6342/NTU.2006.02893

摘要

長期飲用含砷地下水造成之慢性砷中毒影響規模龐大，為全球最重要的公衛議題之一。過去研究認為，人體相關基因對無機砷的代謝具有多形性差異，可能解釋砷暴露相關疾病之個體感受性差異。
無機砷進入體內的代謝過程稱為砷的生物轉化鏈，本研究選取台灣西南部地區280位砷暴露居民進行重疊病例對照試驗，針對代謝鏈上調控基因在樣本族群中之多形性分佈、尿砷代謝指標及砷相關皮膚癌之發生進行相關性研究。研究結果顯示，年齡與環境中砷暴露濃度為皮膚癌發生的重要危險因子，基因多形性的影響則較不顯著。
由基因多形性分析結果，AS3MT單點變異可能影響皮膚癌發生，而GSTO-1與GSTO-2上各變異點之分佈頻率可能受單型影響，其中GSTO-2對尿砷甲基產物影響較為顯著。研究結果認為基因多形性對砷代謝具有影響潛力，有賴更大樣本數對更多基因變異點進行完整的分析，以探討基因調控與個體砷暴露的健康效應。

關鍵字

無機砷暴露 ； 生物轉化 ； 基因多形性 ； AS3MT ； GSTO

並列摘要

Individual variability in human arsenic metabolism has been well discussed in the literature. This variability could also be a candidate determinant of individual susceptibility to arsenic-induced disease in human.
The goal of this study was to investigate the potential role in genetic polymorphisms in association with methylation capacity, as well as with the risk of arsenic-related skin cancer. Genetic association with urinary arsenic metabolite levels and skin cancer status were analyzed in 11 arsenic biotransformation candidate polymorphisms in 280 arsenic-exposure subjects from southeastern Taiwan.
Present data suggested that age and environmental arsenic exposure were both extremely strong risk factors. Compare to GSTO-1, GSTO-2 shows better association with arsenic metabolites, indicating that GSTO-2 may play a role in human As metabolism. In addition, AS3MT involved in As reduction need further study in search of potential effecting polymorphisms. Although the genetic effects remain unclear, the study have provided a framework in which to conduct a larger study to evaluate the potentially susceptibility genes in human arsenicism.

並列關鍵字

arsenic ； biotransformation ； polymorphism ； AS3MT ； GSTO

參考文獻

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