請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17560
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 于明暉(Ming-Whei Yu) | |
dc.contributor.author | Meng-Yin Yeh | en |
dc.contributor.author | 葉孟瑩 | zh_TW |
dc.date.accessioned | 2021-06-08T00:21:12Z | - |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-07-23 | |
dc.identifier.citation | 參考文獻
1. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264-1273. 2. Yu MW, Yang YC, Yang SY, et al. Hormonal markers and hepatitis B virus-related hepatocellular carcinoma risk: a nested case-control study among men. J Natl Cancer Inst. 2001;93(21):1644-1651. 3. Chiu CM, Yeh SH, Chen PJ, et al. Hepatitis B virus X protein enhances androgen receptor-responsive gene expression depending on androgen level. Proc Natl Acad Sci U S A. 2007;104(8):2571-2578. 4. Yeh SH, Chen PJ. Gender disparity of hepatocellular carcinoma: the roles of sex hormones. Oncology. 2010;78(Suppl 1):S172-S179. 5. Zhu R, Zhang JS, Zhu YZ, et al. HBx-induced androgen receptor expression in HBV-associated hepatocarcinoma is independent of the methylation status of its promoter. Histol Histopathol. 2011;26(1):23-35. 6. Wu MH, Ma WL, Hsu CL, et al. Androgen receptor promotes hepatitis B virus-induced hepatocarcinogenesis through modulation of hepatitis B virus RNA transcription. Sci Transl Med. 2010;2(32):32-35. 7. Yu MW, Chang HC, Liaw YF, et al. Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and their relatives. J Natl Cancer Inst. 2000;92(14):1159-1164. 8. Lee MH, Yang HI, Liu J, et al. Prediction models of long-term cirrhosis and HCC risk in chronic hepatitis B patients: Risk scores integrating host and virus profiles. [published online ahead of print March 15, 2013]. Hepatology. 2013; doi: 10.1002/hep.26385. 9. Chemin I, Zoulim F, Merle P, et al. High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology. J Hepatol. 2001;34(3):447-454. 10. Fattovich G, Stroffolini T, Zagni I, et al. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5)(Suppl 1):S35-S50. 11. Tsai FC, Liu CJ, Chen CL, et al. Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinoma. J Viral Hepat. 2007;14(3):153-160. 12. Ikeda K, Saitoh S, Suzuki Y, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol. 1998;28(6):930-938. 13. Lin CW, Lin CC, Mo LR, et al. Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis. J Hepatol. 2013;58(4):730-735. 14. Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology. 2004;127(5)(Suppl 1):S72-S78. 15. Chuang SC, Lee YC, Hashibe M, et al. Interaction between cigarette smoking and hepatitis B and C virus infection on the risk of liver cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010;19(5):1261-1268. 16. Shih WL, Chang HC, Liaw YF, et al. Influences of tobacco and alcohol use on hepatocellular carcinoma survival. Int J Cancer. 2012;131(11):2612-2621. 17. Wu HC, Santella R. The role of aflatoxins in hepatocellular carcinoma. [published online ahead of print October 11, 2012]. Hepat Mon. 2012; doi: 10.5812/hepatmon.7238. 18. Turner PC, Sylla A, Diallo MS, et al. The role of aflatoxins and hepatitis viruses in the etiopathogenesis of hepatocellular carcinoma: A basis for primary prevention in Guinea-Conakry, West Africa. J Gastroenterol Hepatol. 2002;17(Suppl):S441-S448. 19. Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347(3):168-174. 20. Chen CJ, Yang HI, Iloeje UH, et al. Hepatitis B virus DNA levels and outcomes in chronic hepatitis B. Hepatology. 2009;49(5)(Suppl):S72-S84. 21. Yu MW, Yeh SH, Chen PJ, et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J Natl Cancer Inst. 2005;97(4):265-272. 22. Wu CF, Yu MW, Lin CL, et al. Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men. Carcinogenesis. 2008;29(1):106-112. 23. Jardi R, Rodriguez F, Buti M, et al. Mutations in the basic core promoter region of hepatitis B virus. Relationship with precore variants and HBV genotypes in a Spanish population of HBV carriers. J Hepatol. 2004;40(3):507-514. 24. Yotsuyanagi H, Hino K, Tomita E, et al. Precore and core promoter mutations, hepatitis B virus DNA levels and progressive liver injury in chronic hepatitis B. J Hepatol. 2002;37(3):355-363. 25. Chen CH, Changchien CS, Lee CM, et al. Combined mutations in pre-s/surface and core promoter/precore regions of hepatitis B virus increase the risk of hepatocellular carcinoma: a case-control study. J Infect Dis. 2008;198(11):1634-1642. 26. Tong MJ, Blatt LM, Kao JH, et al. Basal core promoter T1762/A1764 and precore A1896 gene mutations in hepatitis B surface antigen-positive hepatocellular carcinoma: a comparison with chronic carriers. Liver Int. 2007;27(10):1356-1363. 27. Liu S, Zhang H, Gu C, et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst. 2009;101(15):1066-1082. 28. Yang HI, Yeh SH, Chen PJ, et al. Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. J Natl Cancer Inst. 2008;100(16):1134-1143. 29. Kramvis A, Kew M, Francois G. Hepatitis B virus genotypes. Vaccine. 2005;23(19):2409-2423. 30. Hadziyannis SJ. Natural history of chronic hepatitis B in Euro-Mediterranean and African countries. J Hepatol. 2011;55(1):183-191. 31. Schaefer S. Hepatitis B virus: significance of genotypes. J Viral Hepat. 2005;12(2):111-124. 32. Yuen MF, Sablon E, Tanaka Y, et al. Epidemiological study of hepatitis B virus genotypes, core promoter and precore mutations of chronic hepatitis B infection in Hong Kong. J Hepatol. 2004;41(1):119-125. 33. Park CH, Jeong SH, Yim HW, et al. Family history influences the early onset of hepatocellular carcinoma. World J Gastroenterol. 2012;18(21):2661-2667. 34. Yeung P, Wong DK, Lai CL, et al. Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B. J Infect Dis. 2011;203(5):646-654. 35. Yuan J, Zhou B, Tanaka Y, et al. Hepatitis B virus (HBV) genotypes/subgenotypes in China: mutations in core promoter and precore/core and their clinical implications. J Clin Virol. 2007;39(2):87-93. 36. Wan DW, Tzimas D, Smith JA, et al. Risk factors for early-onset and late-onset hepatocellular carcinoma in Asian immigrants with hepatitis B in the United States. Am J Gastroenterol. 2011;106(11):1994-2000. 37. Chang PE, Ong WC, Lui HF, et al. Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome. J Gastroenterol. 2008;43(11):881-888. 38. Stevens CE, Neurath RA, Beasley RP, et al. HBeAg and anti-HBe detection by radioimmunoassay: correlation with vertical transmission of hepatitis B virus in Taiwan. J Med Virol. 1979;3(3):237-241. 39. Kim MH, Cha CH, An D, et al. Performance evaluation of Abbott RealTime HBV Quantification Kit for HBV viral load by real-time PCR. Korean J Lab Med. 2008;28(2):144-150. 40. Loeb KR, Jerome KR, Goddard J, et al. High-throughput quantitative analysis of hepatitis B virus DNA in serum using the TaqMan fluorogenic detection system. Hepatology. 2000;32(3):626-629. 41. Ryncarz AJ, Goddard J, Wald A, et al. Development of a high-throughput quantitative assay for detecting herpes simplex virus DNA in clinical samples. J Clin Microbiol. 1999;37(6):1941-1947. 42. Kirschberg O, Schuttler C, Repp R, et al. A multiplex-PCR to identify hepatitis B virus--enotypes A-F. J Clin Virol. 2004;29(1):39-43. 43. Sung FY, Jung CM, Wu CF, et al. Hepatitis B virus core variants modify natural course of viral infection and hepatocellular carcinoma progression. Gastroenterology. 2009;137(5):1687-1697. 44. Hassan MM, Spitz MR, Thomas MB, et al. The association of family history of liver cancer with hepatocellular carcinoma: a case-control study in the United States. J Hepatol. 2009;50(2):334-341. 45. Turati F, Edefonti V, Talamini R, et al. Family history of liver cancer and hepatocellular carcinoma. Hepatology. 2012;55(5):1416-1425. 46. Zhou JY, Zhang L, Li L, et al. High hepatitis B virus load is associated with hepatocellular carcinomas development in Chinese chronic hepatitis B patients: a case control study. Virol J. 2012;9:16. 47. Tai DI, Changchien CS, Hung CS, et al. Replication of hepatitis B virus in first-degree relatives of patients with hepatocellular carcinoma. Am J Trop Med Hyg. 1999;61(5):716-719. 48. Huang HH, Shih WL, Li YH, et al. Hepatitis B viraemia: its heritability and association with common genetic variation in the interferon gamma signalling pathway. Gut. 2011;60(1):99-107. 49. Chou YC, Yu MW, Wu CF, et al. Temporal relationship between hepatitis B virus enhancer II/basal core promoter sequence variation and risk of hepatocellular carcinoma. Gut. 2008;57(1):91-97. 50. Qu L, Kuai X, Liu T, et al. Pre-S deletion and complex mutations of hepatitis B virus related to young age hepatocellular carcinoma in Qidong, China. [published online ahead of print March 28, 2013]. PLoS One. 2013; doi: 10.1371/journal.pone.0059583. 51. Kao JH, Chen PJ, Lai MY, et al. Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology. 2003;124(2):327-334. 52. Baumert TF, Rogers SA, Hasegawa K, et al. Two core promotor mutations identified in a hepatitis B virus strain associated with fulminant hepatitis result in enhanced viral replication. J Clin Invest. 1996;98(10):2268-2276. 53. Kidd AH, Kidd-Ljunggren K. A revised secondary structure model for the 3'-end of hepatitis B virus pregenomic RNA. Nucleic Acids Res. 1996;24(17):3295-3301. 54. Wong GL, Chan HL, Yiu KK, et al. Meta-analysis: The association of hepatitis B virus genotypes and hepatocellular carcinoma. Aliment Pharmacol Ther. 2013;37(5):517-526. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17560 | - |
dc.description.abstract | 摘要
研究背景: 文獻指出,HBeAg、病毒量、基因型和BCP(basal core promoter)雙突變等B型肝炎病毒因子皆與增加罹患肝細胞癌(HCC)之危險有關,然而,鮮有學者探討HBV病毒因子對於早發肝癌(小於50歲發病)之間的關係,此外,在HBV帶原家庭中,病毒因子所影響手足間罹患HCC危險性差異的原因仍不清楚。因此,本研究利用配對病例與未發病手足對照研究來探討此議題。 材料方法: 本研究的個案來自多醫學中心之合作研究計畫。50歲以前即被診斷出肝細胞癌的病例有150位,其中小於40歲之個案有80位。對照組為病例個案之未發病手足,其性別必須與病例個案相同,且年齡差異需小於5歲。共有184位個案符合條件並收為對照組。抽菸情況與飲酒習慣的資料是透過採訪員之問卷所取得,HBV病毒資料來自血液樣本,血清中HBeAg狀態是利用SD BIOLINE HBeAg test kit所測得,另外HBV病毒量、基因型及BCP雙突變的部分則是透過聚合鏈鎖反應(PCR)或即時聚合鏈鎖反應(Real-time PCR)測得。配對之相對危險性(OR)與其95%信賴區間是使用條件式邏輯斯迴歸估計。 結果: HBV相關之病毒因子在經過年齡、抽菸情況、喝酒習慣、HBeAg狀態、病毒量、基因型和BCP雙突變的調整後,只有BCP雙突變有達到統計上之顯著水準。BCP雙突變在經過其他變項調整後之OR為4.01 (95% CI=1.84~8.75,p=0.0005)。其中,發病年齡小於40歲之配對,經過調整後之OR為5.93 (95% CI=2.13~16.49),而40~50歲發病之配對,經調整後之OR為2.43(95% CI=0.79~7.51)。 結論: 本研究在調整家族內HBV病毒感染來源後,證明BCP雙突變對於早發肝癌的發展與HBV帶原家庭中罹患HCC危險性之差異,皆是一個重要的因子。 | zh_TW |
dc.description.abstract | Abstract
Background: Hepatitis B viral factors, including HBeAg positivity, viral load, genotype, and basal core promoter (BCP) double mutations, have been associated with increased risk of hepatocellular carcinoma (HCC). However, few studies have been carried out to explore their role in the development of early-onset HCC diagnosed before age 50. In addition, the effects of these viral factors on the intra-familial difference in the risk of HCC in HBV carriers’s families are unclear. Therefore, we conducted a case-unaffected sibling matched case-control study to address these issues. Materials and Methods: All study subjects were recruited from a multi-center collaboration program on the risk of HCC. Case patients included 150 (80 of whom were diagnosed at equal to or less than 40 years of age) patients with HCC diagnosed at <50 years. All case patients’ unaffected same-sex siblings, who were born within 5 years of the birth of the cases in the same family, were included as control subjects. Totally 184 control subjects were included. Data on smoking status and alcohol consumption were collected from questionnaire by well-trained research assistants at enrollment. Serum HBeAg status was determined by SD BIOLINE HBeAg test kit, while HBV viral load, genotype, and BCP double mutations were assayed by PCR or real-time PCR. Matched odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using conditional logistic regression. Results: Among HBV-related viral factors, only BCP double mutations reached statistical significance after adjustment for age, smoking status, alcohol consumption, HBeAg positivity, viral load, genotype, and BCP double mutations. Overall, the adjusted OR for individuals carrying BCP double mutations was 4.01 (95% CI=1.84~8.75, p=0.0005). The adjusted OR was 5.93 (95% CI=2.13~16.49) for case patients diagnosed 40 years and 2.43(95% CI=0.79~7.51) for case patients diagnosed 40-50 years. Conclusion: We demonstrated that BCP double mutation is a significant determinant for developing early-onset HCC and intrafamilial difference in the risk of HCC in HBV carriers’ families after controlling intrafamilial transmission of HBV. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T00:21:12Z (GMT). No. of bitstreams: 1 ntu-102-R00849001-1.pdf: 992467 bytes, checksum: b16c1aab365f391bed5d91a34dfa0f38 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 目 錄
致謝……………………………………………………………….………...i 中文摘要……………………………………………………………….. …ii 英文摘要………………………………….……………………………….iii 目錄……………………………………………………………….……….v 前言………………………………………………………………………..1 材料與方法………………………………………………………………...6 結果……………………………………………………………….………10 討論……………………………………………………………….……....13 參考文獻………………………………………………………….………18 附錄 | |
dc.language.iso | zh-TW | |
dc.title | B型肝炎病毒之病毒量、基因型及BCP突變在早發肝細胞癌所扮演的角色:手足配對之病例對照研究 | zh_TW |
dc.title | Role of Hepatitis B Virus Load, Genotype, and Basal Core Promoter Mutations in Young-Onset Hepatocellular Carcinoma before Age 50: A Sibling Matched Case-Control Study | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鄭尊仁(Tsun-Jen Cheng),莊雅惠(Ya-Hui Chuang),林志陵(Chih-Lin Lin) | |
dc.subject.keyword | BCP雙突變,早發肝癌,HBV相關病毒因子,HBV基因型,HBV病毒量,手足配對病例對照研究, | zh_TW |
dc.subject.keyword | basal core promoter double mutation,early-onset HCC,hepatitis B viral factor,HBV genotype,HBV viral load,sibling-matched case control study, | en |
dc.relation.page | 27 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2013-07-23 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
顯示於系所單位: | 流行病學與預防醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-102-1.pdf 目前未授權公開取用 | 969.21 kB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。