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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳建仁(Chien-Jen Chen),王根樹(Gen-Shuh Wang) | |
| dc.contributor.author | Yu-Ping Chen | en |
| dc.contributor.author | 陳郁屏 | zh_TW |
| dc.date.accessioned | 2021-06-13T03:17:06Z | - |
| dc.date.available | 2007-08-11 | |
| dc.date.copyright | 2006-08-11 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-30 | |
| dc.identifier.citation | 1. Mass, M.J., et al., Methylated trivalent arsenic species are genotoxic. Chemical Research in Toxicology, 2001. 14(4): p. 355-361.
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Tanaka-Kagawa, T., et al., Functional characterization of two variant human GSTO 1-1s (Ala140Asp and Thr217Asn). Biochemical and Biophysical Research Communications, 2003. 301(2): p. 516-520. 39. Drobna, Z., et al., Metabolism and toxicity of arsenic in human urothelial cells expressing rat arsenic (+3 oxidation state)-methyltransferase. Toxicology and Applied Pharmacology, 2005. 207(2): p. 147-159. 40. Zhang, Y., et al., D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients. Journal of Human Genetics, 2004. 49(6): p. 296-301. 41. Laraqui, A., et al., Influence of methionine synthase (A2756G) and methionine synthase reductase (A66G) polymorphisms on plasma homocysteine levels and relation to risk of coronary artery disease. Acta Cardiologica, 2006. 61(1): p. 51-61. 42. Sebastio, G., et al., The Molecular-Basis of Homocystinuria Due to Cystathionine Beta-Synthase Deficiency in Italian Families, and Report of 4 Novel Mutations. American Journal of Human Genetics, 1995. 56(6): p. 1324-1333. 43. Zhang, G.S. and C.W. Dai, Gene polymorphisms of homocysteine metabolism-related enzymes in Chinese patients with occlusive coronary artery or cerebral vascular diseases. Thrombosis Research, 2001. 104(3): p. 187-195. 44. Tylicki, L., et al., Methylenetetrahydrofolate reductase gene polymorphisms in essential hypertension - Relation with the development of hypertensive end-stage renal disease. American Journal of Hypertension, 2005. 18(11): p. 1442-1448. 45. Adinolfi, L.E., et al., Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C. Hepatology, 2005. 41(5): p. 995-1003. 46. Shen, M., et al., Polymorphisms in folate metabolic genes and lung cancer risk in Xuan Wei, China. Lung Cancer, 2005. 49(3): p. 299-309. 47. Klerk, M., et al., MTHFR 677C -> T polymorphism and risk of coronary heart disease - A meta-analysis. Jama-Journal of the American Medical Association, 2002. 288(16): p. 2023-2031. 48. Deligezer, U., E.E. Akisik, and N. Dalay, Homozygosity at the C677T of the MTHFR gene is associated with increased breast cancer risk in the Turkish population. In Vivo, 2005. 19(5): p. 889-893. 49. Tchounwou, P.B., A.K. Patlolla, and J.A. Centeno, Carcinogenic and systemic health effects associated with arsenic exposure - A critical review, in Toxicologic Pathology. 2003. p. 575-588. 50. Chen, Y.C., et al., Arsenic methylation and skin cancer risk in southwestern Taiwan. Journal of Occupational and Environmental Medicine, 2003. 45(3): p. 241-248. 51. Frosst, P., et al., A Candidate Genetic Risk Factor for Vascular-Disease - a Common Mutation in Methylenetetrahydrofolate Reductase. Nature Genetics, 1995. 10(1): p. 111-113. 52. Nishimura, M., et al., Influence of polymorphisms in the genes for cytokines and glutathione S-transferase omega on sporadic Alzheimer's disease. Neuroscience Letters, 2004. 368(2): p. 140-143. 53. de Jonge, R., et al., Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia. Blood, 2005. 106(2): p. 717-720. 54. Skibola, C.F., et al., Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma. Blood, 2004. 104(7): p. 2155-2162. 55. Yu, L.Z., et al., Genetic variation in genes associated with arsenic metabolism: Glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans. Environmental Health Perspectives, 2003. 111(11): p. 1421-1427. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/31667 | - |
| dc.description.abstract | 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。 | zh_TW |
| dc.description.abstract | 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. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T03:17:06Z (GMT). No. of bitstreams: 1 ntu-95-R93844004-1.pdf: 582715 bytes, checksum: f52079d38df94a74a2bcca488b374aba (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 第一章、前言
1.1 研究背景................................1 1.2 研究目的與架構..........................1 第二章、文獻回顧 2.1 砷的暴露與健康效應......................3 2.2無機砷之胞內作用.........................3 2.3 無機砷之生物轉化鏈......................4 2.3.1五價無機砷之還原反應................5 2.3.2 三價砷之甲基化反應.................6 2.3.3 五價砷之還原反應...................7 2.4輔助砷代謝的類胱胺酸代謝鏈相關酵素.......8 2.5 砷之甲基化代謝反應與健康危害............8 2.6 砷暴露之個體易感受性差異................9 2.6.1 物種差異.............................10 2.6.2 族群差異.............................10 2.6.3 個體間變異...........................10 2.7基因多型性對甲基化代謝活性之影響潛力....11 2.7.1砷之生物轉換鏈...................11 2.7.2類胱胺酸代謝鏈...................12 第三章、實驗材料與方法 3.1 研究地區...............................18 3.2 研究對象...............................18 3.3 研究方法...............................19 3.3.1人口學資料的蒐集.................19 3.3.2井水中含砷量測定.................19 3.3.3個人砷暴露量評估.................19 3.3.4尿中砷含量測定...................20 3.3.5尿中砷代謝產物與代謝能力評估指標.20 3.3.6血液DNA分離...........................21 3.3.7基因多型性鑑定........................21 3.3.8資料分析與統計方法...............23 第四章、結果與討論 4.1基本資料分析............................25 4.2環境暴露與個體代謝指標分析..............30 4.3基因多型性與皮膚癌發生..................37 4.4基因多型性與尿中砷代謝指標..............40 4.5環境暴露量與基因多型性之交互作用........45 4.6 GSTO基因之單型分析.....................48 第五章、結論與建議.........................53 第六章、參考文獻...........................56 | |
| dc.language.iso | zh-TW | |
| dc.subject | GSTO | zh_TW |
| dc.subject | 無機砷暴露 | zh_TW |
| dc.subject | 生物轉化 | zh_TW |
| dc.subject | 基因多形性 | zh_TW |
| dc.subject | AS3MT | zh_TW |
| dc.subject | arsenic | en |
| dc.subject | GSTO | en |
| dc.subject | AS3MT | en |
| dc.subject | polymorphism | en |
| dc.subject | biotransformation | en |
| dc.title | 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 | zh_TW |
| dc.title | Genetic polymorphisms associated with arsenic methylation and skin cancer risk in southwestern Taiwan | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 薛玉梅(Yu-Mei Hsueh),黃耀輝,吳美滿 | |
| dc.subject.keyword | 無機砷暴露,生物轉化,基因多形性,AS3MT,GSTO, | zh_TW |
| dc.subject.keyword | arsenic,biotransformation,polymorphism,AS3MT,GSTO, | en |
| dc.relation.page | 60 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-31 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 環境衛生研究所 | zh_TW |
| 顯示於系所單位： | 環境衛生研究所 | |
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