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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳燕惠(Yen-Hui Chen) | |
dc.contributor.author | Yi-An Wu | en |
dc.contributor.author | 吳以安 | zh_TW |
dc.date.accessioned | 2021-06-17T01:22:02Z | - |
dc.date.available | 2022-09-08 | |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-10 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67167 | - |
dc.description.abstract | 研究背景
在先前的研究中顯示喝酒可能增加大腸直腸癌的發生風險,而酒精代謝酶之特定基因型可能增加大腸直腸癌發生的風險,而此風險可能在酒精代謝酶活性差異較大的亞洲族群更為增加;至今研究酒精與酒精代謝酶之基因多型性與大腸直腸癌關係之研究數量有限,且尚未有一致的結論,台灣更缺少這樣的研究資料,因此希望藉由本研究,釐清大腸直腸癌在台灣族群的風險因子,包括酒精代謝酶之基因多型性與相關的環境因子等,以達到及早防範大腸直腸癌發生的目的。 研究目的 探討台灣族群中,酒精代謝酶之基因多型性與大腸直腸癌風險的相關性,及基因多型性與生活環境因子間交互作用對於大腸直腸癌風險之可能影響。 研究方法 本研究設計採病例對照研究(case-control study),依據所定納入及排除條件篩選受試者。研究對象分為病例組及對照組,前者乃大腸直腸癌確診之門診病人、後者係未罹病之家屬。受試者相關資料之收集,包括基本資料、生活型態資料及周邊靜脈血液,後者係供進行alcohol dehydrogenase (ADH)、aldehyde dehydrogenase (ALDH)與cytochrome P450 2E1 (CYP2E1)基因的單核苷酸多型性分析。除描述性統計與單變項分析外,本研究進一步運用多元邏輯斯迴歸分析(multiple logistic regression analysis)檢定各變項與大腸直腸癌風險相關性,以勝算比(odds ratio)及百分之九十五信賴區間(95% confidence interval)表示之。本研究經倫理委員會通過執行。 研究結果 本研究納入臺大醫院73位大腸直腸癌的病患及67位相對應病例組病患的家屬。研究發現,飲酒、高血壓及年紀為大腸直腸癌的獨立危險因子,其勝算比及95%信賴區間分別為2.93 (1.31-6.52, p=0.0086)、2.61 (1.04-6.54, p=0.0412)及1.07(1.04-1.11, p<0.0001)。ADH1B rs1042026 與ADH1A rs1230025 突變的基因型均與大腸直腸癌風險增高相關,其勝算比及95%信賴區間分別為3.58 (1.05-12.22, p=0.0417)及2.58 (1.09-6.09, p=0.0305)。與帶有野生基因型且不飲酒者相比,飲酒者若帶有ADH1B rs1229984、ADH7 rs17028973 及ADH7 rs284787 突變的基因型,皆有較高的大腸直腸癌風險;除此之外,ADH1A rs1230025、ADH1B rs1042026、ALDH2 rs671、CYP2E1 rs12031920 及CYP2E1 rs3813867 無論帶有野生基因型或突變基因型,飲酒者得病風險皆較高,若帶有突變基因型且飲酒者,風險則更高。 結論 本研究證實飲酒、高血壓及年紀為台灣族群大腸直腸癌的獨立危險因子,並發現ADH1A rs1230025 與ADH1B rs1042026 的基因變異是重要的危險因子,而飲酒則會更加重罹患大腸直腸癌的風險。 | zh_TW |
dc.description.abstract | Background
According to the statistic reports from International Agency for Research on Cancer (IARC), the incidence and mortality rate of colorectal cancer (CRC) ranked third and fourth, respectively, among ten most commonly diagnosed cancer worldwide. Moreover, based on the statistics from Health Promotion Administration, Ministry of Health and Welfare in Taiwan, the incidence and mortality rate of CRC ranked second and third, respectively, among all cancers in Taiwanese population. However, if CRC is diagnosed and treated in early phase, the 5-year survival rate for stage I CRC can be up to 90%; on the other hand, the 5-year survival rate for end stage CRC is only approximately 10%. Therefore, the screening, early diagnosis of CRC is crucial. There are some known risk factors for CRC, including familial adenomatous polyposis, obesity, physical inactivity, etc. Alcohol had also been identified as an important risk factor among Asian population because of the reduced enzymatic activity of some of the alcohol metabolizing enzymes. Through this study, we try to examine the risk factors of CRC among Taiwanese population, including alcohol metabolizing enzyme gene polymorphisms and their interactions with environmental factors, so as to attain the early prevention of CRC. Study objective The purpose of this study is to assess the impact of alcohol metabolizing enzyme gene polymorphisms, alcohol consumption and their interactions with the risk of CRC in Taiwanese. Methods This is a case-control study. Data collected from the study subjects include baseline characteristics, lifestyle information and venous blood of each subject for analysis of gene polymorphisms of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and cytochrome P450 2E1 (CYP2E1). The odds ratios (OR) and their corresponding 95% confidence intervals (CI) of the risk factors were calculated for the risk of CRC using logistic regression models. Results A case group of 73 colorectal cancer patients and 67 family members of the case group defined as the control group were enrolled according to the inclusion and exclusion criteria in our study. Alcohol consumption, hypertension and age were identified as independent risk factors for CRC with the ORs and 95% CI 2.93 (1.31-6.52, p=0.0086), 2.61 (1.04-6.54, p=0.0412) and 1.07 (1.04-1.11, p<0.0001). Risk alleles of ADH1B (rs1042026) and ADH1A (rs1230025) were associated with CRC. The alcohol drinkers with variant alleles of ADH1B (rs1042026) and ADH1A (rs1230025) had higher risk of CRC with the ORs and 95 % CI 8.94 (2.58-30.91, p=0.0005) and 7.18 (1.96-26.31, p=0.0029) when compared to the non-drinkers with wildtype alleles. Conclusions Alcohol consumption, hypertension and age are independent risk factors for CRC. The variations of ADH1B rs1042026 and ADH1A rs1230025 are associated with the risk of CRC in Taiwanese. Alcohol consumption increases the risk of CRC in the subjects carrying the risk alleles. | en |
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dc.description.tableofcontents | 誌謝………………………………………………………….….………………….... i
中文摘要……………………………………………………….…………………… ii Abstract...………………………………………………………….…………………. iv 目錄………………………………………………………….………………………. vi 表目錄…………………………………………………………….…………...……. ix 圖目錄…………………………………………………………….………………... x 英文名詞與縮寫對照表………………………………………….………………..... xi 第1章 緒論 1 1.1 大腸直腸癌之流行病學現況 1 1.2 大腸直腸癌之風險因子與個體基因感受性 1 1.3 研究目的 5 第2章 研究方法與材料 7 2.1 研究設計與對象 7 2.2 檢體收集與處理方法 8 2.2.1 血液樣本處理 8 2.2.2 去氧核醣核酸檢體萃取 8 2.3 單核苷酸多型性的選擇與基因型鑑定 10 2.3.1 單核苷酸多型性的選擇 10 2.3.2 基因型鑑定 10 2.4 統計分析 11 第3章 研究結果 13 3.1 研究對象基本特徵 13 3.2 危險因子與大腸直腸癌發生之關係 14 3.2.1 單變項邏輯斯迴歸分析 14 3.2.2 多變項邏輯斯迴歸分析 15 3.3 研究對象基因型分布 15 3.4 單核苷酸多型性與大腸直腸癌發生之關係 15 3.4.1 對照組為無血緣關係之次族群分析 16 3.4.2 對照組為有血緣關西之次族群分析 16 3.5 基因多型性與喝酒易臉潮紅之關係 16 3.6 基因多型性與環境因子之交互作用 17 3.6.1 基因多型性與環境因子對於大腸直腸癌風險之關係 17 3.6.2 基因多型性與環境因子及喝酒臉潮紅對於大腸直腸癌風險之關係 18 第4章 討論 19 4.1 研究的主要發現 19 4.1.1 大腸直腸癌的危險因子 19 4.1.2 基因多型性與大腸直腸癌風險關係 19 4.1.3 基因多型性與飲酒對於大腸直腸癌風險關係 19 4.1.4 基因多型性與喝酒易臉潮紅的關係 20 4.1.5 基因多型性與飲酒及飲酒後臉潮紅於大腸直腸癌風險關係 20 4.2 與其他類似研究之差異性 22 4.2.1 大腸直腸癌的危險因子 22 4.2.2 基因多型性與大腸直腸癌風險關係 23 4.2.3 基因多型性與飲酒對於大腸直腸癌風險關係 25 4.2.4 基因多型性與喝酒易臉潮紅的關係 26 4.2.5 基因多型性與飲酒及飲酒後臉潮紅於大腸直腸癌風險關係 26 4.3 研究優勢 27 4.4 研究限制 27 第5章 結論與未來展望 29 5.1 結論 29 5.2 未來展望 29 圖表 30 參考文獻 59 附錄 67 附錄一 台灣常見酒精濃度、容量對照表 67 附錄二 受試者同意書 68 附錄三 研究結果附表 77 表S1. 本研究所選定SNP與大腸直腸癌發生風險之單變項迴歸分析 77 表S2. 本研究所選定SNP與大腸直腸癌發生風險之多變項迴歸分析 83 表S3. 本研究所選定SNP與大腸直腸癌發生之相關性(對照組為無血緣關係) 89 表S4. 本研究所選定SNP與大腸直腸癌發生之相關性(對照組為有血緣關係) 95 表S5. 本研究所選定SNP與喝酒是否易臉潮紅之相關性 101 表S6. 基因型與飲酒對於大腸直腸癌風險之交互作用影響 107 表S7. 基因型與飲酒與臉潮紅對於大腸直腸癌風險之交互作用影響 123 | |
dc.language.iso | zh-TW | |
dc.title | 酒精與酒精代謝酶之基因多型性於大腸直腸癌風險的影響 | zh_TW |
dc.title | Alcohol Intake, Gene Polymorphisms of Alcohol Metabolizing
Enzymes and the Risk of Colorectal Cancer | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 何?芳(Yunn-Fang Ho) | |
dc.contributor.oralexamcommittee | 謝銘鈞(Ming-Jun Xie),吳宜珍(Yi-Zhen Wu) | |
dc.subject.keyword | 酒精,酒精代謝?,大腸直腸癌,單核?酸多型性, | zh_TW |
dc.subject.keyword | alcohol,alcohol metabolizing enzyme,single nucleotide polymorphism,colorectal cancer, | en |
dc.relation.page | 128 | |
dc.identifier.doi | 10.6342/NTU201702460 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-08-10 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床藥學研究所 | zh_TW |
顯示於系所單位: | 臨床藥學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
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ntu-106-1.pdf 目前未授權公開取用 | 1.43 MB | Adobe PDF |
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