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研究生:黃喬婷
研究生(外文):Huang, Chiao-Ting
論文名稱:細胞色素P4502E1、甲烯基四氫葉酸還原酵素基因多形性和肝細胞癌之重疊病例對照研究
論文名稱(外文):Genetic Polymorphisms in Cytochrome P450 2E1 and Methylenetetrahydrofolate Reductase and Risk of Hepatocellular Carcinoma-- A Nested Case-Control Study
指導教授:陳建仁陳建仁引用關係于明暉于明暉引用關係---
指導教授(外文):Chen Chien-JenYu Ming-Whei
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:1998
畢業學年度:86
語文別:中文
論文頁數:82
中文關鍵詞:肝細胞癌細胞色素P450 2E1基因多形性甲烯基四氫葉酸還原酵素基因多形性
外文關鍵詞:hepatocellular carcinomacytochrome P450 2E1 polymorphismmethylenetetrahydrofolate reductase polymorphism
相關次數:
  • 被引用被引用:2
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遺傳易感性對癌症發展之獨立作用及其與環境中因子的交互作用, 近年來已在癌症研究
領域受到廣泛深入的討論. 本研究採重疊病例對照研究法探討細胞色素
P4502E1(cytochrome
P450 2E1, CYP2E1)與甲烯基四氫葉酸還原酵素(methylenetetrahydrofolate reductase,
MTHFR)基因多形性對肝細胞癌的影響. 研究世代包括7342名民國七十七年
至八十一年在公保
聯合門診中心及長庚醫院肝病中心收案的世代成員, 世代成員進入研究即
接受問卷訪視和血
液檢體採集.CYP2E1與MTHFR基因多形性是利用以聚合酵素連鎖反應為基礎
的限制片段長度多
形性進行分析,共有80位病例、437位對照個案成功的鑑定出CYP2E1-RsaI
基因型; 76位HBsAg
陽性病例和163位HBsAg陽性對照個案鑑定出MTHFR基因型. 研究結果發現
在控制HBsAg帶原狀
態及其他危險因子後, c1/c1基因型者和其他基因型者比較的危險對比值
為2.0(95%信賴區間
1.1-3.5). 抽菸、喝酒習慣對CYP2E1基因多形性和肝細胞癌不具修飾作
用. 但CYP2E1 c1/c1
基因型與抽菸、喝酒習慣一起分析其協同作用時, 和不具c1/c1基因型者
比較,只有喝酒且抽
菸之c1/c1 基因型者的危險對比值達統計顯著意義. 另外, 慢性肝病史、一等親肝癌史和
CYP2E1基因多形性對罹患肝細胞癌也具有累加模式的協同作用, 和未曾罹
患慢性肝病且不具
c1/c1基因型者比較, 曾罹患慢性肝病且為c1/c1基因型者的危險對比值高
達18.5(95%信賴區
5.2-65.6); 和沒有一等親肝癌史且不具c1/c1基因型者比較,有一等親肝
癌史且為c1/c1基因
型者的危險對比值為4.9(95%信賴區間1.7-14.5). 在MTHFR基因多形性方
面, MTHFR與肝細胞
癌沒有統計顯著相關, 但與肝膽疾病史具有累加模式的交互作用, 和未曾
罹患肝膽疾病且不
具val/val基因型者比較, 曾罹患肝膽疾病且為val/val基因型者的危險對
比值高達10.3(95%
信賴區間1.1-95.6). CYP2E1和MTHFR基因多形性也具有顯著累加模式的協
同作用, 最高危險
對比值出現在CYP2E1 c1/c1基因型且為MTHFR val/val基因型的組別.
Objectives. The relationship between genetic polymorphisms in enzymes
involved in nutrient/carcinogen metabolism and risk of cancer has recently
received attention. This study was carried out to investigate whether
cytochrome P450 2E1 (CYP2E1) and methylenetetrahydrofolate reductase (MTHFR)
genetic polymorphisms were related to susceptibility to hepatocellular
carcinoma (HCC). Methods. Genotyping of CYP2E1 was performed using polymerase
chain reaction-based restriction fragment length polymorphism on peripheral
leukocyte DNA from 80 HCC cases and 437 controls nested within a cohort study
of 7342 men. A total of 76 HBsAg-positive HCC cases and 163 HBsAg-positive
controls were also tested for MTHFR genetic polymorphism.
Results. The adjusted
odds ratio (OR) for the CYP2E1 predominant homozygous c1/c1 genotype detected
by RsaI digestion was 2.0 (95% confidence interval [CI]1.1-3.5). There was no
notable interaction between CYP2E1 polymorphism and cigarette smoking or
alcohol drinking in HCC risk compared with individuals having the heterozygous
genotype c1/c2 or rare genotype c2/c2; however, significantly elevated HCC risk
was found only among homozygotes of c1/c1 genotype who had habits of smoking
and drinking. A synergistic effect on HCC risk was observed for the susceptible
genotype of CYP2E1 with chronic liver disease and a family history of HCC in
first degree relatives. No overall association between MTHFR genetic
polymorphism and HCC was observed, but MTHFR val/val genotype interacts with
the history of liver diseases and CYP2E1 genotype. The most striking OR for HCC
was obverved among chronic hepatitis B carriers with the variant homozygous
val/val genotype of MTHFR and past history of liver diseases (OR=10.3, 95%CI
1.1-95.6). Conclusions. Homozygosity for the c1/c1 genotype of CYP2E1 was
associated with increased risk of HCC. This study suggested that further
evaluation of MTHFR genetic polymorphism as a susceptibility factor for HCC is
warranted.
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