請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53076
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 | Wen-Jie Liu | en |
dc.contributor.author | 劉彣潔 | zh_TW |
dc.date.accessioned | 2021-06-15T16:42:56Z | - |
dc.date.available | 2020-09-14 | |
dc.date.copyright | 2015-09-14 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-08-11 | |
dc.identifier.citation | 1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61(2):69-90. 2. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132(7):2557-76. 3. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012;142(6):1264-1273 e1. 4. Chen CJ, Liang KY, Chang AS, et al. Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma. Hepatology 1991;13(3):398-406. 5. Jee SH, Ohrr H, Sull JW, et al. Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J Natl Cancer Inst 2004;96(24):1851-6. 6. Ross RK, Yuan JM, Yu MC, et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 1992;339(8799):943-6. 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):1159-64. 8. Turati F, Edefonti V, Talamini R, et al. Family history of liver cancer and hepatocellular carcinoma. Hepatology 2012;55(5):1416-25. 9. Nguyen VT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. J Viral Hepat 2009;16(7):453-63. 10. Yu MW, Chen CJ. Hepatitis B and C viruses in the development of hepatocellular carcinoma. Crit Rev Oncol Hematol 1994;17(2):71-91. 11. 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):1644-51. 12. Bruix J, Sherman M, Practice Guidelines Committee AAftSoLD. Management of hepatocellular carcinoma. Hepatology 2005;42(5):1208-36. 13. 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. 14. Park CH, Jeong SH, Yim HW, et al. Family history influences the early onset of hepatocellular carcinoma. World J Gastroenterol 2012;18(21):2661-7. 15. 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):881-8. 16. Kim JH, Choi MS, Lee H, et al. Clinical features and prognosis of hepatocellular carcinoma in young patients from a hepatitis B-endemic area. J Gastroenterol Hepatol 2006;21(3):588-94. 17. Kulis M, Esteller M. DNA methylation and cancer. Adv Genet 2010;70:27-56. 18. Bollati V, Schwartz J, Wright R, et al. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev 2009;130(4):234-9. 19. Zhu ZZ, Hou L, Bollati V, et al. Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemiol 2012;41(1):126-39. 20. Sarter B, Long TI, Tsong WH, et al. Sex differential in methylation patterns of selected genes in Singapore Chinese. Hum Genet 2005;117(4):402-3. 21. Boks MP, Derks EM, Weisenberger DJ, et al. The relationship of DNA methylation with age, gender and genotype in twins and healthy controls. PLoS One 2009;4(8):e6767. 22. Breitling LP, Yang R, Korn B, et al. Tobacco-smoking-related differential DNA methylation: 27K discovery and replication. Am J Hum Genet 2011;88(4):450-7. 23. Bleich S, Lenz B, Ziegenbein M, et al. Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation of its mRNA expression in patients with alcohol dependence. Alcohol Clin Exp Res 2006;30(4):587-91. 24. Moore LE, Huang WY, Chung J, et al. Epidemiologic considerations to assess altered DNA methylation from environmental exposures in cancer. Ann N Y Acad Sci 2003;983:181-96. 25. Bjornsson HT, Sigurdsson MI, Fallin MD, et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA 2008;299(24):2877-83. 26. Fraga MF, Ballestar E, Paz MF, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 2005;102(30):10604-9. 27. Barry KH, Moore LE, Sampson J, et al. DNA methylation levels at chromosome 8q24 in peripheral blood are associated with 8q24 cancer susceptibility loci. Cancer Prev Res (Phila) 2014;7(12):1282-92. 28. Shen L, Ahuja N, Shen Y, et al. DNA methylation and environmental exposures in human hepatocellular carcinoma. J Natl Cancer Inst 2002;94(10):755-61. 29. Shitani M, Sasaki S, Akutsu N, et al. Genome-wide analysis of DNA methylation identifies novel cancer-related genes in hepatocellular carcinoma. Tumour Biol 2012;33(5):1307-17. 30. Revill K, Wang T, Lachenmayer A, et al. Genome-wide methylation analysis and epigenetic unmasking identify tumor suppressor genes in hepatocellular carcinoma. Gastroenterology 2013;145(6):1424-35 e1-25. 31. Terry MB, Delgado-Cruzata L, Vin-Raviv N, et al. DNA methylation in white blood cells. Epigenetics 2014;6(7):828-837. 32. Delgado-Cruzata L, Wu HC, Perrin M, et al. Global DNA methylation levels in white blood cell DNA from sisters discordant for breast cancer from the New York site of the Breast Cancer Family Registry. Epigenetics 2012;7(8):868-74. 33. Wong EM, Southey MC, Fox SB, et al. Constitutional methylation of the BRCA1 promoter is specifically associated with BRCA1 mutation-associated pathology in early-onset breast cancer. Cancer Prev Res (Phila) 2011;4(1):23-33. 34. Widschwendter M, Apostolidou S, Raum E, et al. Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. PLoS One 2008;3(7):e2656. 35. Villanueva A, Portela A, Sayols S, et al. DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma. Hepatology 2015;61(6):1945-56. 36. Yeh M-Y. 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. Unpublished master thesis. National Taiwan University, Taipei, Taiwan. 2013. 37. 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):1134-43. 38. Pawlik TM, Delman KA, Vauthey JN, et al. Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 2005;11(9):1086-92. 39. Huang J, Zhao YL, Li Y, et al. Genomic and functional evidence for an ARID1A tumor suppressor role. Genes Chromosomes Cancer 2007;46(8):745-50. 40. Rabizadeh S, Xavier RJ, Ishiguro K, et al. The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death. J Biol Chem 2004;279(28):29247-54. 41. Lambert MP, Paliwal A, Vaissiere T, et al. Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake. J Hepatol 2011;54(4):705-15. 42. Um TH, Kim H, Oh BK, et al. Aberrant CpG island hypermethylation in dysplastic nodules and early HCC of hepatitis B virus-related human multistep hepatocarcinogenesis. J Hepatol 2011;54(5):939-47. 43. Calvisi DF, Ladu S, Gorden A, et al. Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. J Clin Invest 2007;117(9):2713-22. 44. Frost RJ, Hamra FK, Richardson JA, et al. MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs. Proc Natl Acad Sci U S A 2010;107(26):11847-52. 45. Zheng K, Wang PJ. Blockade of pachytene piRNA biogenesis reveals a novel requirement for maintaining post-meiotic germline genome integrity. PLoS Genet 2012;8(11):e1003038. 46. Su PF, Lee TC, Lin PJ, et al. Differential DNA methylation associated with hepatitis B virus infection in hepatocellular carcinoma. Int J Cancer 2007;121(6):1257-64. 47. Park IY, Sohn BH, Yu E, et al. Aberrant epigenetic modifications in hepatocarcinogenesis induced by hepatitis B virus X protein. Gastroenterology 2007;132(4):1476-94. 48. Zhu YZ, Zhu R, Shi LG, et al. Hepatitis B virus X protein promotes hypermethylation of p16(INK4A) promoter through upregulation of DNA methyltransferases in hepatocarcinogenesis. Exp Mol Pathol 2010;89(3):268-75. 49. Becker SA, Lee TH, Butel JS, et al. Hepatitis B virus X protein interferes with cellular DNA repair. J Virol 1998;72(1):266-72. 50. Shim Y-H, Yoon G-S, Choi H-J, et al. p16 Hypermethylation in the early stage of hepatitis B virus-associated hepatocarcinogenesis. Cancer Letters 2003;190(2):213-219. 51. Hunt CM, McGill JM, Allen MI, et al. Clinical relevance of hepatitis B viral mutations. Hepatology 2000;31(5):1037-44. 52. Lin X, Xu X, Huang QL, et al. Biological impacts of 'hot-spot' mutations of hepatitis B virus X proteins are genotype B and C differentiated. World J Gastroenterol 2005;11(30):4703-8. 53. Guo X, Jin Y, Qian G, et al. Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China. J Hepatol 2008;49(5):718-25. 54. 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):265-72. 55. Chen G, Lin W, Shen F, et al. Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study. Am J Gastroenterol 2006;101(8):1797-803. 56. Lee S, Lee HJ, Kim J-H, et al. Aberrant CpG Island Hypermethylation Along Multistep Hepatocarcinogenesis. The American Journal of Pathology 2003;163(4):1371-1378. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53076 | - |
dc.description.abstract | 研究背景:肝細胞癌大部分是由慢性HBV感染所導致。目前早發肝細胞癌的病因不明瞭且缺乏適當的生物標記,DNA甲基化會受到基因、環境和臨床前期疾病的影響,因此DNA甲基化或許能解釋手足間罹患早發肝細胞癌風險的差異,但目前DNA甲基化和早發肝細胞癌的關係仍未知。本研究使用手足配對樣本去探討血液DNA甲基化和HBV導致的早發性肝癌之間的相關性。 材料與方法:本研究使用手足配對病例對照研究,包括134位早發性肝細胞癌患者和174位他們的未罹病手足做為對照個案,早發肝細胞癌的定義為發病年齡50歲或以下。我們採用兩階段的研究設計,第一階段由小樣本(包括48個病例和59個對照)篩選九個標記,顯著或重要的五個標記再進行擴大分析,我們使用的DNA是由白血球中所萃取,透過焦磷酸定序來量化甲基化的程度。 結果:在校正干擾因子包括年齡和BCP雙突變後,我們發現在3個探針標的的序列上,有9個CpG位點的DNA甲基化和肝細胞癌呈現顯著的負相關,以最顯著的CpG位點而言,隨甲基化四分位數下降,肝細胞癌的相對危險性指標(95%信賴區間)各為1.00、4.23(1.27-14.15)、13.73(3.43-54.99)和47.68(10.49-216.74)。我們也發現五個和肝細胞癌有關的CpG位點和HBV基因型、病毒量或BCP雙突變有關,此外,兩個和肝細胞癌有關的CpG位點也分別和血清α-胎兒蛋白濃度及腫瘤大小有關。 結論:白血球上的甲基化標記可能和早發性肝細胞癌罹病或預後有關,而且這些甲基化標記可能參與HBV導致肝細胞癌的過程,這些標記或許能用作肝細胞癌的罹病風險預測或預後指標,但未來仍需要前瞻性研究來證明這些標記的可用性。 | zh_TW |
dc.description.abstract | Introduction: Hepatocellular carcinoma (HCC) is mostly attributed to chronic HBV infection. However, cause of early-onset HCC is unclear and there is not an appropriate biomarker to detect early-onset HCC at present. DNA methylation is a dynamic change affected by genetics, environments and preclinical diseases. Therefore, DNA methylation may interpret the difference in risk of early-onset HCC between siblings, but the correlation between DNA methylation and early-onset HCC is unknown. In this study, we use case-sibling matched study to determine whether DNA methylation in leukocytes is associated with early-onset HCC in relation to HBV. Materials and Methods: We used case-sibling matched study involving a total of 134 early-onset HCC cases (ages of diagnosis with HCC were less than or equal to 50 years of age) and 174 their unaffected siblings. We used two-stage study design to select candidate methylation markers. 48 matched sets (including 48 cases and 59 sibling controls) were used for screening nine candidate methylation markers, and five significant or important markers were then tested for remaining study subjects. DNA was extracted from buffy coat, and methylation levels were quantified by using pyrosequencing. Results: Methylation on three probes targeting sequences included 9 CpG sites were significantly inversely related to HCC after adjusting for age and BCP double mutation. In most significant CpG site, odds ratios (95% CI) of HCC were increased with decreasing quartiles of methylation levels, which were 1.00, 4.23 (1.27-14.15), 13.73 (3.43-54.99), and 47.68 (10.49-216.74). We also found that five HCC-related CpG sites were associated with HBV genotype, viral load or BCP double mutation. In addition, two HCC-related CpG sites were associated with serum α-fetoprotein levels and HCC tumor size, respectively. Conclusions: We confirmed that methylation markers measured on leukocytes were associated with early-onset HCC or prognosis of HCC, and these markers may contribute to risk of HCC by coordinating with HBV. In addition, these markers also have potential to use as HCC risk assessment or prognostic biomarkers of HCC. However, prospective studies are still needed in the future to determine the availability of these markers. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T16:42:56Z (GMT). No. of bitstreams: 1 ntu-104-R02849023-1.pdf: 972982 bytes, checksum: 25ff369cfcf9a9d7ae3f3379b176f0a4 (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | Introduction…………………………………………………………………………………………………………………………1 Materials and Methods…………………………………………………………………………………………………7 Database…………………………………………………………………………………………………………………………7 Study Subjects and Design……………………………………………………………………………8 Laboratory Analysis……………………………………………………………………………………………8 Statistical Analysis…………………………………………………………………………………………9 Results……………………………………………………………………………………………………………………………………10 Discussion……………………………………………………………………………………………………………………………13 References……………………………………………………………………………………………………………………………19 | |
dc.language.iso | en | |
dc.title | DNA 甲基化和早發肝細胞癌之關聯性:手足配對之病例對照研究 | zh_TW |
dc.title | Relationship between DNA Methylation and Early-Onset Hepatocellular Carcinoma: Case-Sibling Matched Study | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 薛玉梅,鄭尊仁,劉俊人 | |
dc.subject.keyword | 早發肝細胞癌,DNA 甲基化,白血球, | zh_TW |
dc.subject.keyword | early-onset HCC,DNA methylation,leukocytes, | en |
dc.relation.page | 31 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2015-08-11 | |
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-104-1.pdf 目前未授權公開取用 | 950.18 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。