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研究生:江創騰
研究生(外文):CHIANG CHUANG-TENG
論文名稱:臺灣肺癌病人之CYP2A6基因多型性分析研究
論文名稱(外文):The polymorphisms of CYP2A6 among Taiwan lung cancer patients
指導教授:姜泰安姜泰安引用關係
指導教授(外文):CHIANG TAI-AN
學位類別:碩士
校院名稱:中華醫事學院
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文出版年:2006
畢業學年度:93
語文別:中文
論文頁數:50
中文關鍵詞:肺癌基因多型性細胞色素P450 2A6
外文關鍵詞:lung cancerCYP2A6polymorphism
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中文摘要
自西元 1982 年以來,惡性腫瘤便成為國人十大死因中的第一位。根據衛生署 2004 年公佈的資料顯示,肺癌更是高居國人癌症死亡率之冠,許多研究顯示肺癌的發生與暴露環境中的致癌物質有關。例如多環芳香烴類化合物 (polycyclic aromatic hydrocarbons,PAH )。PAH 是一種廣泛分布於環境中的汙染物,例如:香菸煙霧懸浮微粒,空氣懸浮微粒,廚房中烹飪時所產生的油煙及二手煙。細胞色素P450 (cytochrome P 450,CYP) 這群酵素正是體內代謝這些有毒物質的酵素群之ㄧ。而 cytochrome P450 2A6 (CYP2A6) 主要是代謝香菸中特殊的致癌物質 nitrosamines 的酵素之ㄧ。先前許多研究顯示, CYP2A6 之基因多型性與肺癌的發生風險有關,尤其是抽菸相關性肺癌。因此,本研究總共收集了 121 位肺癌的病人, 105 位肺部疾患之病人以及 108 位健康的成年人。利用 polymerase chain reaction - based restriction fragment length polymorphism (PCR-RFLP) 之方法來探討CYP2A6基因多型性與肺癌以及肺病之間的相關性。
在這研究中發現在台灣人這個族群中 CYP2A6 基因多型性可能與肺癌之發生風險有關,尤其是帶有 CYP2A6*1B 此基因型的人,有1.94 倍的風險會導致肺癌 (95% 信賴區間為1.29-2.92),而有 2.64倍的風險會罹患 Squamous cell carcinoma (95% 信賴區間為1.46-4.75),而有 1.93 倍之風險會罹患 Adenocarcinoma (95% 信賴區間為 1.12-3.33),其他肺癌組織型中並無顯著差異。而 Genotype 雖有較高的風險會得到肺癌但未達統計顯著意義,可能的原因是樣本數較少,未達統計效力所致。然而,CYP2A6 之基因多型性在肺癌的發生風險上仍然扮演著重要的角色。
Abstract
Since 1982, the cancer has become the 1st leading cause of death in Taiwan. According to the announcement material showed by the Department of Health in 2004, lung cancer high occupies the first of the cause of cancer death, lung cancer occurrence related with the exposed environment carcinogen in many research, for example polycyclic aromatic hydrocarbon compound (PAH). PAH is one of the pollutants distributed in the environment, for example: suspended particle of tobacco, suspended particle in air, the soot from home cooking and
second-hand smoke.
Cytochrome P450 (CYP) is one of this enzyme groups which metabolized these toxicant in vivo. Cytochrome P450 2A6 (CYP2A6) is one of major enzymes to metabolize tobacco specific carcinogen ex.: nitrosamines. Many research showed that the genetic polymorphisms of CYP2A6 related with lung cancer risk, especially tobacco-induced lung cancer. Therefore, this study had collected 121 lung cancer patients, 105 lung disease patients and 108 healthy adults. To study the relationship between genetic polymorphisms of CYP2A6 gene and lung cancer risk by using polymerase chain reaction – based restriction fragment length
polymorphism (PCR-RFLP).
In this study, we discovered the genetic polymorphisms of CYP2A6 were possible association with lung cancer risk in the Taiwanese. People who had the CYP2A6*1B gene had 1.94 time of risks to cause lung cancer (95% C.I. is 1.29-2.92), but had 2.64 time of risks to affect Squamous cell carcinoma (95% C.I. is 1.46-4.75), and had 1.93 time of risks to affect Adenocarcinoma (95% C.I. is 1.12-3.33), there were no significance difference in other histology type of lung cancer. But the genotypes of CYP2A6 were no significance difference; this might because we didn’t have enough samples in our study, so it didn’t have sufficient statistical power. In conclusion, the genetic polymorphism of CYP2A6 still played an important role in the lung cancer risk.
目錄
頁次
研究生口試委員會審定書 i
博碩士論文電子檔案上網授權書 ii
博碩士論文授權書 iii
中文摘要 iv
英文摘要 vi
誌謝 viii
目錄 ix

第一章 文獻回顧 1
第一節 肺癌簡介 1
第二節 致癌物質代謝酵素 4
第三節CYP 簡介 5
第二章 研究目的 9
第三章 材料與方法 10
第一節 檢體收集 10
第二節 Genomic DNA 之抽取 10
第三節 Polymerase Chain Reaction (PCR) 12
第四節 電泳分析 14
第五節 限制片段長度多型性分析(RFLP) 16
第六節 DNA訂序代工單位 19
第四章 結果 20
第五章 討論 23
第六章 結論 27
參考文獻 28
附錄

圖表目錄
Table1. 2004 the ten causes of death for cancer in Taiwan…………………………...36

Table 2. The characteristic of human CYPs………………………………………….37

Table 3. Human CYP families and their main functions………………………...........38

Table 4. The genetic polymorphism in the CYP2A6 gene…………………………...39

Table 5. Characteristics of lung cancer patients and control subjects…………...……40

Table 6. Difference in distribution of CYP2A6 genotypes in patients………………..41

Table 7. Association between CYP2A6 polymorphism and risk for lung cancer cell type……………………………………………………………………..…………….42

Table 8. Difference in distribution of CYP2A6 genotypes in smoker………………..43

Fig 1. The cutting site for BstU-I………………………………………………….…44

Fig 2. The cutting site for Bsu36-I…………………………………………………...44

Fig 3. The human genomic DNA of CYP2A6 by polymerase chain reaction………..45

Fig 4. Genotyping of CYP2A6*1A, CYP2A6*1B, CYP2A6*4 allele in human genomic DNA of CYP2A6 by polymerase chain reaction-restriction fragment length polymorphism………………………………………………………...………………46

Fig 5. Schematic structures of CYP2A7 and CYP2A6 genes…………………………47

Fig 6. The sequences for CYP2A6*1A allele………………………………………...48

Fig 7. The sequences for CYP2A6*1B allele………………………………………...49

Fig 8. The sequences for CYP2A6*4 allele………………………………………….50
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陳建仁:台灣重要癌症之分子流行病學研究,第二十九屆國軍軍醫學術研討會專題討論專刊,2002.

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