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研究生:陳伯任
研究生(外文):Po-Jen Chen
論文名稱:基質金屬蛋白酶-1,-2,-3,-7基因多形性與台灣地區大腸直腸癌的感受性
論文名稱(外文):Polymorphisms of the matrix metalloproteinase-1,-2,-3,-7 and colorectal cacer risk in Taiwan
指導教授:謝玲玲謝玲玲引用關係
指導教授(外文):Ling-Ling Hsieh
學位類別:碩士
校院名稱:長庚大學
系所名稱:基礎醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:78
中文關鍵詞:基質金屬蛋白酶大腸直腸癌多形性
外文關鍵詞:matrix metalloproteinaseMMPcolorectal cancerpolymorphismSNP
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基質金屬蛋白酶(Matrix metalloproteinases,MMPs)是一種需要鋅離子的內切肽酶,這類的蛋白酶家族結構上具有高度的保留性。它們具有水解細胞外基質(extracellular matrix,ECM)的功能,因此MMPs被認為在腫瘤的入侵與轉移時扮演很重要的角色,同時發現MMPs會在腫瘤組織過量表現。先前的研究指出,MMPs啟動子區單一核苷酸多形性(single nucleotide polymorphisms,SNPs)會影響基因的轉錄能力,進而影響MMPs的表現量,所以此多形性也許會與腫瘤的感受性有某種程度的相關性。本論文針對MMP1、2、3、7四個基因,試圖探索這些MMPs基因啟動子單一核苷酸多形性與台灣地區大腸直腸癌感受性的相關性。我們利用PCR-RFLP分析MMP1啟動子-1607與MMP7啟動子-181基因多形性,同時利用MALDI-TOF Mass分析MMP2啟動子-1306與MMP3啟動子-1612基因多形性。初步結果顯示,在大腸直腸癌病例組與對照組間,四種MMPs的基因型分布並未達到顯著差異。然而在分層分析的部分,我們發現有喝咖啡習慣者,MMP1啟動子基因型為2G/2G (高轉錄活性)型者罹患大腸直腸癌的風險明顯較1G/2G+1G/1G者高(OR=6.75,95% CI=1.19-46.73,P=0.01)。此外我們也發現大腸直腸癌的黏液型腫瘤個案,MMP7 A/G+G/G(高轉錄活性)基因型的比率較非黏液型高(OR=2.6,95% CI= 1.18-5.38,P<0.01);然而MMP7 A/G+G/G(高轉錄活性)基因型者三年內復發的機率較A/A型者為低(OR=0.42,95% CI= 0.18-0.90,P=0.02)。
Matrix metalloproteinases (MMPs) are a family of highly conserved zinc-dependent endopeptidases that degrade different components of extracellular matrix (ECM) and play important roles in tumor invasion and metastases. Overexpression of MMPs has been demonstrated in many human tumors. Recent studies indicated that MMPs promoter single nucleotide polymorphisms (SNPs) could affect transcriptional activity resulting in protein expression levels. Thus, polymorphisms of MMPs may associate with cancer susceptibility to certain extent. This thesis tried to explore the associations between the polymorphisms of MMP1, 2, 3, 7 and the risk of colorectal cancer in Taiwan. MMP1 (-1607, 1G/2G) and MMP7 (-181, A/G) polymorphisms were genotyped by PCR-RFLP analysis, while genotypes of MMP2 (-1306, C/T) and MMP3 (-1612, 5A/6A) were determined by MALDI-TOF Mass analysis. Our preliminary results showed that the distribution of these 4 MMPs genotypes was not statistically different between colorectal cancer patients and healthy controls. However, stratification analysis found that the MMP1 2G/2G (high transcriptional activity) genotype was associated with a higher risk of colorectal cancer among coffee-drinkers (OR=6.75, 95% CI=1.19-46.73, P=0.01). Furthermore, the frequency of the MMP7 A/G and G/G (high transcriptional activity) genotype was significantly higher in colorectal cancer patients with mucinous tumor than those with non-mucinous tumor (OR=2.6, 95% CI= 1.18-5.38, P<0.01). However, the patients with MMP7 A/G and G/G (high transcriptional activity) genotype had lower 3-year recurrent rate than those with A/A (low transcriptional activity) genotype (OR=0.42,95% CI= 0.18-0.90,P=0.02).
目錄
中文摘要 vi
英文摘要 viii
第一章 前言 1
第二章 文獻探討 2
第一節 大腸直腸癌簡介 2
第二節 基質金屬蛋白酶(MMPs)簡介 5
第三節 MMPs啟動子區域的SNPs與癌症的相關性研究 8
第四節 研究動機與目的 14
第三章 材料與方法 15
第一節 研究對象與生物檢體 15
第二節 實驗分析方法 16
第四章 結果 26
第一節 人口學與生活習慣分布 26
第二節 MMPs啟動子基因型與大腸直腸癌感受性的相關性 27
第三節 大腸直腸癌危險因子與基因型的交互作用 29
第四節 MMPs啟動子基因型與大腸直腸癌臨床病理特徵的相關性 31
第五章 討論 33
第六章 結論 37
附表 38
附圖 61
參考文獻 63
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