飲酒情形與醇脫氫酶和醛脫氫酶的基因多型性與食道癌及胃癌之相關性研究

Interactive Effects of Lifetime Alcohol Consumption and Alcohol and Aldehyde Dehydrogenase Polymorphisms on Esophageal and Gastric Cancer Risks

陳韻如(Yun-Ju Chen)

指導教授 ： 吳明蒼

高雄醫學大學/健康科學院/職業安全衛生研究所/碩士(2005年)

摘要

酒精為引起腸胃道疾病的一個重要危險因子，在人體內主要經由
醇脫氫酶 (ADH2) 將乙醇代謝成乙醛，再由醛脫氫酶 (ALDH2) 將乙醛代謝成乙酸，因此本研究將探討飲酒，酒精代謝酵素醇脫氫酶和醛脫氫酶之基因多型性與食道癌及胃癌之相關性。
本研究設計採用醫院為主的病例對照研究法，自民國89年8月至93年6月，收集台大醫院及高雄榮民總醫院與高雄醫學大學附設中和醫院，經由醫生診斷確定為新發生食道癌之患者330位為病歷組，其對照組來自相同醫院的健康檢查，診斷無癌症病史之個案共592位；並收集來自高雄醫學大學附設中和醫院，新發生胃癌之患者140位為病歷組，其對照組來自相同醫院的健康檢查，診斷無癌症病史之個案共383位；並以年齡 (±4歲) 及性別進行配對 (病歷組：對照組=1:1~4)。利用聚合脢連鎖反應方法判斷ADH2與ALDH2基因型。
本研究在調整過有關的干擾因子之後，結果發現個案帶ADH2*1/*1基因型者，相較於帶ADH2*2/*2基因型者，罹患食道癌的危險性為3.99倍 (95%CI, 2.13-7.48)；同時，個案帶ALDH2*1/*2 及 ALDH2*2/*2基因型者，相較於帶ALDH2*1/*1基因型者，罹患食道癌的危險性分別為4.99及 4.24倍 (95% CI, 3.11-7.99 及 1.52-11.84)，並進一步發現ADH2及ALDH2的基因多型性與飲酒習慣對於食道癌的發生存在交互作用。但是，並未發現ADH2與ALDH2的基因多型性與胃癌的發生有顯著相關性。
本研究結果顯示酒精代謝酵素 (ADH2與ALDH2) 的基因多型性會調節酒精代謝而影響食道癌之發生，但是與胃癌則未有顯著的相關性。

關鍵字

醛脫氫? ； 醇脫氫? ； 胃癌 ； 食道癌 ； 基因多型性

並列摘要

In this study, we investigated the association between the genetic polymorphisms of ADH2 and ALDH2 and esophageal and gastric cancer risks in the Taiwanese population. A hospital-based case-control study was conducted in Taiwan. Between August, 2000 and June, 2004, 330 newly-diagnosed esophageal squamous cell carcinoma and 592 controls were recruited from National Taiwan University Hospital (NTUH), Kaohsiung Medical University Hospital (KMUH) and Kaohsiung Veterans General Hospital (KVGH). In addition, 140 newly-diagnosed gastric cancer and 383 controls were recruited from KMUH. Controls were matched to the cases by age (±4 years) and sex (cases: controls=1: 1~4). The ADH2 and ALDH2 polymorphisms were genotyped by the method of PCR-RFLP.
Individuals with ADH2*1/*1 had a 3.99-fold risk (95% CI = 2.13-7.48) to develop esophageal cancer than those with ADH2*2/*2, after adjusted for appropriate covariates. Individuals with ALDH2*1/*2 and ALDH2*2/*2 had 4.99- (95% CI = 3.11-7.99) and 4.24-fold risk (95% CI = 1.52-11.84), respectively, to develop esophageal cancer than those with ALDH2*1/*1, after adjusted for appropriate covariates. We also found an interactive risk of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk. Similar significant effects of ADH2 and ALDH2 on esophageal cancer risk were also found, when categorized by different drinking statuses. In contrast, no significant effect of those two polymorphisms on gastric cancer risk was noted. Those results suggest that ADH2 and ALDH2 polymorphisms play a pivotal role to modify the effect of lifetime alcohol consumption on esophageal cancer, but not on gastric cancer risk.

並列關鍵字

esophageal cancer ； aldehyde dehydrogenase ； alcohol dehydrogenase ； gastric cancer ； genetic polymorphisms

參考文獻

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