醇去氫脢(ADH2)與醛去氫脢(ALDH2)之基因多型性與台灣男性食道癌之相關性研究

The Relationship Between Genetic Polymorphisms of Alcohol and Aldehyde Dehydrogenases and Esophageal Squamous Cell Carcinoma Risk in Males

吳佳芳(Chia-Fang Wu)

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(2004年)

摘要

目的：本研究目的在探討飲酒習慣、酒精代謝酵素(醇去氫脢ADH2 和醛去氫脢ALDH2)的基因多型性與台灣男性食道癌三者間的相關性。

方法：本研究設計採用醫院為主的病例對照研究法，從民國89年8月至92年6月，總共自高雄榮民總醫院及高雄醫學大學附設中和醫院收集134位診斷為鱗狀上皮細胞癌之男性食道癌病人為病例組，237位男性健康檢查無罹患癌症之年齡配對(±4歲)為對照組。利用聚合脢連鎖反應(PCR)放大特定基因片段後，以限制片段長度多型性(RFLP)來判斷ADH2與ALDH2之基因多型性。

結果：本研究在調整過可能的干擾因子之後發現，相對於基因型ADH2*2/*2，個案帶有ADH2*1/*2和ADH2*1/*1基因型者其危險比分別為2.28(95%CI：1.11-4.68)和7.14(95%CI：2.76-18.46)；此顯著增加的危險性亦發現在相對於基因型ALDH2*1/*1，個案帶有ALDH2*1/*2基因型者其危險比為5.25(95%CI：2.47-11.19)。此外，當我們合併兩個基因型後亦發現在相對於ADH2*1/*2或ADH2*2/*2及ALDH2*1/*1，個案帶有ADH2*1/*1及ALDH2*1/*2者其危險比更高達36.79(95%CI：9.36-144.65)。同時，在多變項邏輯氏迴歸分析中發現ADH2和ALDH2基因多型性與飲酒習慣間具有交互作用的影響存在。

結論：本研究結果顯示ADH2*1/*1和ALDH2*1/*2的基因型會影響飲酒與食道癌發生的相關性。藉由此結果可以發現國人罹患食道癌之高危險群以做為日後篩檢和預防的重要參考。

關鍵字

食道癌、醇去氫脢、醛去氫脢、基因多型性

並列摘要

Objective：The association between genetic polymorphisms of ADH2 and ALDH2, lifetime alcohol consumption and esophageal cancer risk was investigated in the Taiwanese men.

Method：A hospital-based case-control study was conducted between August, 2000 and June, 2003. In total, 134 pathologically-proven esophageal squamous cell carcinoma male patients and 237 male controls were recruited from Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital in southern Taiwan. ADH2 and ALDH2 polymorphisms were genotyped using a method of PCR-RFLP.

Results：Compared to those with ADH2*2/*2, individuals with ADH2*1/*2 and ADH2*1/*2 had 2.28- and 7.14-fold, respectively, increased risk to develop esophageal cancer (95% CI = 1.11-4.68 and 2.76-18.46) after adjusting for alcohol consumption and other covariates. The significant increased risk was also noted among subjects with ALDH2*1/*2 (Adjusted OR (AOR) = 5.25, 95% CI = 2.47-11.19), when compared to those with ALDH2*1/*1. The increased risk of esophageal cancer was even strengthen, when subjects carried both ADH2*1/*1 and ALDH2*1/*2, compared to those with ADH2*1/*2 or ADH2*2/*2 and ALDH2*1/*1 (AOR=36.79, 95%CI=9.36-144.65). In addition, a multiplicative effect of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk was noted.

Conclusion：Our results suggest polymorphisms of ADH2 and ALDH2 can modify the influence of alcoholic consumption on esophageal cancer risk. These findings can be used to identify the more susceptible subpopulation for esophageal cancer.

並列關鍵字

genetic polymorphisms ； esophageal cancer ； alcohol dehydrogenase ； aldehyde dehydrogenase

參考文獻

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