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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 Alcohol Intake, Gene Polymorphisms of Alcohol Metabolizing Enzymes and the Risk of Colorectal Cancer |
Authors: | Yi-An Wu 吳以安 |
Advisor: | 陳燕惠(Yen-Hui Chen) |
Keyword: | 酒精,酒精代謝?,大腸直腸癌,單核?酸多型性, alcohol,alcohol metabolizing enzyme,single nucleotide polymorphism,colorectal cancer, |
Publication Year : | 2017 |
Degree: | 碩士 |
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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67167 |
DOI: | 10.6342/NTU201702460 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 臨床藥學研究所 |
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