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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 于明暉 | |
dc.contributor.author | Li-Ching Chang | en |
dc.contributor.author | 張儷瀞 | zh_TW |
dc.date.accessioned | 2021-06-08T05:18:12Z | - |
dc.date.copyright | 2005-08-04 | |
dc.date.issued | 2005 | |
dc.date.submitted | 2005-07-29 | |
dc.identifier.citation | 1.Cancer Registry Annual Report, Republic of China, 1998.
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Mutation of nucleotide 1,762 in the core promoter region during hepatitis B e seroconversion and its relation to liver damage in hepatitis B e antigen carriers. Journal of Medical Virology 1998;55:185-90. 26.Melegari M, Scaglioni PP, Wands JR. The small envelope protein is required for secretion of a naturally occurring hepatitis B virus mutant with PreS1 deleted. Journal of Virology 1997;71:5449-54. 27.Xu Z, Yen TS. Intracellular retention of surface protein by a hepatitis B virus mutant that releases virion particles. Journal of Virology 1996;70:133-40. 28.Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL, Palmiter RD. Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice. Cell 1989;59:1145-56. 29.Huang SN, Chisari FV. Strong, sustained hepatocellular proliferation precedes hepatocarcinogenesis in hepatitis B surface antigen transgenic mice. Hepatology 1995;21:620-6. 30.Wang HC, Wu HC, Chen CF, Fausto N, Lei HY, Su IJ. Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific PreS mutants that may induce endoplasmic reticulum stress. American Journal of Pathology 2003;163:2441-9. 31.Chang WW, Su IJ, Lai MD, Chang WT, Huang W, Lei HY. The role of inducible nitric oxide synthase in a murine acute hepatitis B virus (HBV) infection model induced by hydrodynamics-based in vivo transfection of HBV-DNA. Journal of Hepatology 2003;39:834-42. 32.Fan YF, Lu CC, Chen WC, Yao WJ, Wang HC, Chang TT, Lei HY, Shiau AL, Su IJ. Prevalence and significance of hepatitis B virus (HBV) PreS mutants in serum and liver at different replicative stages of chronic HBV infection. Hepatology 2001;33:277-86. 33.Hsieh YH, Su IJ, Wang HC, Chang WW, Lei HY, Lai MD, Chang WT, Huang W. PreS mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage. Carcinogenesis 2004;25:2023-32. 34.Ogura Y, Kurosaki M, Asahina Y, Enomoto N, Marumo F, Sato C. Prevalence and significance of naturally occurring mutations in the surface and polymerase genes of hepatitis B virus. Journal of Infectious Diseases 1999;180:1444-51. 35.Chen HB, Fang DX, Li FQ, Jing HY, Tan WG, Li SQ. A novel hepatitis B virus mutant with A-to-G at nt551 in the surface antigen gene. World Journal of Gastroenterology 2003;9:304-8. 36.Locarnini S. Molecular virology of hepatitis B virus. Seminars in Liver Disease 2004;24 Suppl 1:3-10. 37.Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000--summary of a workshop.[see comment]. Gastroenterology 2001;120:1828-53. 38.Lai CL, Chien RN, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, Wu PC, Dent JC, Barber J, Stephenson SL, Gray DF. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.[see comment]. New England Journal of Medicine 1998;339:61-8. 39.Hur GM, Lee YI, Suh DJ, Lee JH. Gradual accumulation of mutations in precore core region of HBV in patients with chronic active hepatitis: implications of clustering changes in a small region of the HBV core region. Journal of Medical Virology 1996;48:38-46. 40.Breslow NE, Day NE. Design considerations. Statistical methods in Cancer Research. Lyoncedex, France: International Agency for Research on Cancer, 1987. 41.Kao JH. Hepatitis B viral genotypes: clinical relevance and molecular characteristics. Journal of Gastroenterology & Hepatology 2002;17:643-50. 42.Liu CJ, Kao JH, Chen PJ, Lai MY, Chen DS. Molecular epidemiology of hepatitis B viral serotypes and genotypes in taiwan. Journal of Biomedical Science 2002;9:166-70. 43.Orito E, Ichida T, Sakugawa H, Sata M, Horiike N, Hino K, Okita K, Okanoue T, Iino S, Tanaka E, Suzuki K, Watanabe H, Hige S, Mizokami M. Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan. Hepatology 2001;34:590-4. 44.Kao JH, Chen PJ, Lai MY, Chen DS. Sequence analysis of PreS/surface and pre-core/core promoter genes of hepatitis B virus in chronic hepatitis C patients with occult HBV infection. Journal of Medical Virology 2002;68:216-20. 45.Huy TT, Ushijima H, Quang VX, Win KM, Luengrojanakul P, Kikuchi K, Sata T, Abe K. Genotype C of hepatitis B virus can be classified into at least two subgroups. Journal of General Virology 2004;85:283-92. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/24196 | - |
dc.description.abstract | 背景:HBV病毒因子與肝細胞癌的關係近年來著重在HBV DNA與基因型層面。本研究目的在利用重疊病例對照研究分析病例和對照組在PreS/S及其和P基因重疊區域各點核苷酸變異分佈的情形,同時考慮基因型的影響。方法:研究個案來自一個1988-1992年間收案之男性HBV帶原者世代,對照組是依照病例進入研究年齡及血液採檢時間進行個別匹配,共計86名病例和125名對照進入分析。對於追蹤期間的血液檢體分析,是選擇病例發病兩年內之血液檢體,對照則取與病例檢體距離最近時點之血液檢體分析,共計17名病例與27名對照個案。結果:以adw為參考序列和對照組基線血液檢體分析結果進行比對,發現8個頻率在20%以上的變異型,包括PreS1區的2989C、3050T、3097A、3174T、PreS2區35A、S區的285A、529G、586C。B基因型序列大多數位置之核苷酸型態和adw序列一致,只有在A2989C、C3050T、C3174T與S區的A529G處具有盛行率在20%以上的變異型。基因型C在整段序列的許多位置,均具有盛行率在20%以上的變異型,尤其在PreS2和S基因區域nt 85-nt 598,變異型頻率可達50%以上,病例組和對照組在頻率分佈上具顯著差異的位置到處可見,高差異區主要分布在PreS2的nt 76-nt 147處,顯著差異位置包括A76C、G85A、G87A、C93T、A96C、A99C 、T105C、T109A和G110C,變異型頻率差異在15.3%-30.40%。這些病例和對照組具顯著差異的位置對B基因型者而言,變異型的頻率均在6.3%以下,但對C基因型者而言,變異型頻率均介於37.1%-62.9%,因此再單就C基因型者分析這些核苷酸位置變異和HCC的關係,結果發現在nt 76-nt 110及nt 619處與HCC仍舊具有邊緣性統計相關。分析兩時點間序列的差異,發現大部分位置均處穩定狀態,只有nt 2898、nt 3174和nt 529具有大於20%以上的突變率。結論:B基因型大致反映adw序列,而C基因型病毒序列在各核苷酸位置和adw序列比較具較多變異。HBV PreS/S及與其重疊P基因區,各核苷酸位置在追蹤期間大致處於相當穩定狀態,以adw為參考序列,病例與對照組比較具變異型頻率較高,且分散在全區域,但高差異區集中在PreS2 區nt 76-nt 110處,和已知〝a〞determinant區域重疊。 | zh_TW |
dc.description.abstract | Background and Aim: Variations in the viral genome of hepatitis B virus (HBV) has been associated with the clinical outcome of chronic HBV infection, but the significance of these variations in the development of hepatocellular carcinoma (HCC) remains largely unknown. The aim of this study was to longitudinally analyze the nucleotide variations in the PreS/S and overlapping P gene regions of the HBV genome and HCC risk.
Materials and Methods: Direct sequencing of HBV gene was performed on plasma samples from 86 cases and 125 controls nested within a cohort of HBV male carriers recruited between 1988-1992. Controls were matched with cases on the age of entering the study and the time of collection of blood samples at baseline. We also performed sequencing of the HBV gene in plasma samples collected from a total of 17 cases and 27 controls during follow-up. At the second time point, for cases, blood samples collected within two years before the onset of HCC were used. For controls, measuring time was selected according to the nearest blood collecting time of cases. Results: Compared with adw as the reference sequence, 8 variants were found to have a frequency of ≧ 20% including 2989C, 3050T, 3097A, 3174T in PreS1 region, 35A in PreS2 region, and 285A, 529G, 586C in S region, at baseline samples of controls, the sequence of genotype B was mostly consistent with the adw sequence, except A2989C, C3050T, C3174T and A529G, which occurred at frequency of ≧ 20%. For genotype C, many positions in S region had variant types with prevalence ≧ 20%, especially at nt 85-nt 598 in PreS/S region, the frequency of variant type was ≧ 50%. Difference in nucleotide substitution between case and control groups was everywhere, high variant region was mainly at nt 76-nt 147 in PreS2, which contained 9 variants (including A76C, G85A, G87A, C93T, A96C, A99C, T105C, T109A and G110C) with frequency differences of 15.3%-30.40%. Differences in positions between case and control groups were lower than 6.3% for genotype B. The corresponding figure for genotype C was 37.1%-62.9%. When analysis was limited to these variant positions were still marginally statistically significantly associated with HCC subjects with genotype C. Comparing blood samples at baseline and those at follow-up, higher rate (defined as ≧ 20%) for nucleotide change during follow-up was only observed at three positions nt 2898,nt 3174 and nt 529. Conclusions: Genotype B was mostly consistent with adw sequence, while genotype C had much more variations compared with adw sequence. In most of the PreS/S and overlapping P gene region, nucleotide change was infrequent during long-term follow-up period. Compared with controls, cases had more variant types and high variant region was mainly at nt 76-nt 110 in PreS2 region, where lies within 〝a〞 determinant of HBsAg. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T05:18:12Z (GMT). No. of bitstreams: 1 ntu-94-R92842007-1.pdf: 816905 bytes, checksum: c5f18858525b603493857bd9a513fafd (MD5) Previous issue date: 2005 | en |
dc.description.tableofcontents | 背景及研究動機………………………………………………… 1
材料與方法……………………………………………………… 4 研究設計………………………………………………………… 4 研究追蹤世代…………………………………………………… 4 病例和對照組…………………………………………………… 5 實驗室分析……………………………………………………… 6 統計方法………………………………………………………… 7 結果……………………………………………………………… 8 病例組和對照組基本資料……………………………………… 8 PreS/S與重疊P區域核苷酸變異分佈……………………………8 PreS/S與重疊P區域核苷酸變異追蹤……………………………9 PreS/S與重疊P區域核苷酸變異和基因型與HCC間危險相關…10 討論………………………………………………………………10 參考文獻…………………………………………………………14 表一 病例組和對照組基線資料特徵………………………………18 表二 在C基因型下,HBV PreS/S及重疊P區域變異與HCC的關係…19 圖一 以HBV adw-pODW282為基準,對照組在HBV PreS1/PreS2基 因區各點變異型頻率分佈……………………………………20 圖二 以HBV adw-pODW282為基準,對照組在HBV S基因區各點變異 型頻率分佈……………………………………………………21 圖三 以HBV adw-pODW282為基準,對照組在HBV S基因區各點變異 型頻率分佈……………………………………………………22 圖四 以對照組為基準,病例和對照組在HBV PreS/S全基因區各點 變異型頻率差異………………………………………………23 圖五 以對照組為基準,病例與對照組在HBV PreS1/S2基因區各點 變異型頻率差異………………………………………………24 圖六 以對照組為基準,病例組與對照組在HBV S基因區各點變異型 頻率差異………………………………………………………25 圖七 以對照組為基準,病例組與對照組在HBV S基因區各點變異型 頻率差異………………………………………………………26 圖八 以參考序列為基準,追蹤期間各變異點上核苷酸型態變化頻 率………………………………………………………………27 圖九 以HBV adw-pODW282為基準,C基因型中各點變異型分佈頻率… …………………………………………………………………28 圖十 以HBV adw-pODW282為基準,非C基因型中各點變異型分佈頻率 …………………………………………………………………29 附錄 ……………………………………………………………30 實驗方法…………………………………………………………30 附錄表……………………………………………………………36 附錄圖……………………………………………………………39 | |
dc.language.iso | zh-TW | |
dc.title | B型肝炎病毒Surface基因和重疊Polymerase基因區域之突變頻譜和肝細胞癌危險性:重疊病例對照研究 | zh_TW |
dc.title | Mutations in Surface and Overlapping Polymerase Gene Region of Hepatitis B virus and Risk of Hepatocellular Carcinoma: A Nested Case-Control Study | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳建仁,蕭朱杏,李文宗,潘文涵 | |
dc.subject.keyword | B型肝炎病毒,surface基因,polymerase基因, | zh_TW |
dc.subject.keyword | Hepatitis B virus,surface gene,polymerase gene, | en |
dc.relation.page | 41 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2005-08-01 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 流行病學研究所 | zh_TW |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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