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研究生:蕭亦琮
研究生(外文):shiao yi-tzone
論文名稱:H-ras1稀有小衛星基因和B型肝炎引起之肝細胞癌的關係:在散發和家族病例之致癌過程中的角色
論文名稱(外文):H-ras1 Rare Minisatellite Alleles and Hepatitis B-Related Hepatocellular Carcinoma:Role in Induction of Sporadic and Familial Cancers
指導教授:陳建仁陳建仁引用關係于明暉于明暉引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:流行病學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:67
中文關鍵詞:肝細胞癌H-ras1小衛星基因B型肝炎
外文關鍵詞:Hepatocellular CarcinomaH-ras1 Minisatellite AllelesHepatitis B virus
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目的:本研究利用病例對照研究法探討H-ras1小衛星(minisatellite) 稀有基因和B型肝炎帶原者罹患肝細胞癌危險性的關係,強調H-ras1小衛星稀有基因是否在散發和家族病例的致癌過程中扮演不同的角色。方法:研究個案包括126名具一等親肝細胞癌家族史病例、238名散發病例和177名對照個案。全部個案均為B型肝炎表面抗原陽性個案。利用ABI 377 DNA自動定序儀之基因掃描軟體進行H-ras1小衛星基因重複序列分析,利用定序分析確認基因掃描結果的基因型。稀有基因的定義為a1以外的其他基因。結果:對照組、散發病例和家族病例的稀有基因頻率分別為0.16、0.22和0.20。家族病例和散發病例在稀有基因數目的分佈無顯著差異。無論是散發病例組或家族病例組相較於對照組,調整或不調整進入研究年齡、性別、籍貫、抽煙和喝酒習慣,稀有基因和肝細胞癌的危險對比值均未達統計顯著意義。對性別和抽煙習慣進行H-ras1小衛星稀有基因和肝細胞癌關係的分層分析也未發現顯著相關。以年齡和喝酒習慣進行分層分析,調整危險因子後,發現稀有基因的作用只有在特殊組別達到顯著意義,在50歲以上者,家族病例和對照組比較,帶兩個稀有基因者的危險對比值為4.9 (95%信賴區間:1.1-21.9, p=0.036);在無喝酒習慣者中,家族病例和對照組比較,帶兩個稀有基因者的危險對比值為3.0 (95%信賴區間:1.0-8.6, p=0.045)。結論:無強烈證據顯示H-ras1稀有基因在B型肝炎帶原者發展為肝細胞癌的過程中扮演一個重要的角色,雖然本研究無法排除此基因可能在特殊族群具有作用存在。
Objectives : The aims of this study were to investigate the relationship of H-ras1 rare minisatellite alleles and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk, with emphasis on their roles in induction of sporadic and familial HCC. Methods : We conducted a case-control study of 364 HCC case subjects (comprising 126 familial case subjects who had at least one first-degree relative affected with HCC, and 238 sporadic case subjects) and 177 control subjects. All subjects were HBV carriers. We sized H-ras1 minisatellite alleles with an Applied Biosystems model 377 automated DNA sequencer and GENESCANTM software. Numbers of the 28-bp tandem repeat were confirmed by direct DNA sequencing. Alleles other than a1 were considered ‘rare’. Results : The frequency of all the H-ras1 minisatellite rare alleles combined in control subjects, sporadic case subjects and familial case subjects was 0.16, 0.22 and 0.20, respectively. There was no significant difference in the rare allele frequency between the familial and sporadic case subjects. We found no association of rare allele with HCC, before or after adjustment for risk factors and irrespective of which group of case subjects (familial or sporadic) were compared with control subjects. Stratification by sex and status of cigarette smoking also failed to reveal any association. However, the effect of rare alleles was different between older and younger subjects. Among subjects > 50 years, familial case subjects were found to carry two rare alleles more frequently than control subjects (adjusted odds ratio [OR]=4.9, 95% confidence interval [CI]=1.1-21.9); whereas no association was observed among younger subjects. There was no association between rare alleles and HCC among habitual alcohol drinkers. However, among nondrinkers, the effect of rare allele on HCC risk was significant when compared familial case subjects with control subjects. Conclusions : Our data do not provide strong evidence that H-ras1 rare minisatellite alleles have a role in the etiology of HCC, although we can not exclude an effect in a small subgroup.
目錄……………………………………………………………………………..i
圖表目錄……………………………………………………………………….ii
中文摘要………………………………………………………………………..1
英文摘要………………………………………………………………………..2
第一章前言………………………………………………………………………………3
第二章文獻探討
第一節描述流行病學特徵………………………………………………………..4
第二節危險因子研究……………………………………………………………...5
第三節以往和HCC有關的基因研究……………………………………..…12
第四節ras基因和訊息傳導路徑………………………………………………15
第五節ras基因突變和癌症的相關研究……………………………………..16
第六節H-ras1小衛星基因多形性及其功能………………………………...18
第七節H-ras1小衛星基因多形性與癌症的相關研究……………………19
第三章材料與方法
第一節研究個案…………………………………………………………………...27
第二節實驗方法…………………………………………………………………...29
第三節資料處理及統計方法……………………………………………………32
第四章結果……………………………………………………………………………...37
第五章討論……………………………………………………………………………...54
參考文獻……………………………………………………………………………………59
圖表目錄
圖3-1 第一次PCR後基因掃描……………………………………………………,……33
圖3-2 nested-PCR後基因掃描……………………………………………...…….……...34
圖3-3 a1基因重複序列定序…………………………………………………….………..35
圖4-1 a1基因之基因掃描結果鹼基對數的分佈……………………...………………47
圖4-2 a1-1基因之基因掃描結果鹼基對數的分佈…………………...………………48
圖4-3 a1-2基因之基因掃描結果鹼基對數的分佈……………...……………………49
表2-1 H-ras1小衛星基因重複序列多形性和癌症之相關性研究.………………..22
表4-1 多發病例組、單發病例組和對照組之人口學特徵分佈……………………41
表4-2 喝酒習慣在多發病例組、單發病例組和對照組之分佈……………………42
表4-3 抽煙習慣在多發病例組、單發病例組和對照組之分佈……………………44
表4-4 H-ras1基因頻率在多發病例組、單發病例組和對照組之分佈……..……46
表4-5 稀有基因在多發病例組、單發病例組和對照組之分佈……………………50
表4-6 多發指標病例一等親HCC罹病數和稀有基因的關係……………………..50
表4-7 稀有基因在多發病例組、單發病例組和對照組之分佈:依年齡分組…51
表4-8 稀有基因在多發病例組、單發病例組和對照組之分佈:依性別分組…52
表4-9 稀有基因在多發病例組、單發病例組和對照組之分佈:依喝酒分組…53
表4-10 稀有基因在多發病例組、單發病例組和對照組之分佈:依抽煙分組..53
中華民國八十六年癌症登記
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