Alcohol Metabolism Genes May Modify Risk of Esophageal Cancer From Drinking

Polymorphisms of alcohol and aldehyde dehydrogenase (ADH1B and ALDH2) have been associated with an increased risk of esophageal cancer. Researchers in Taiwan aimed to confirm this association and determine whether lifetime alcohol use modifies it. They compared demographic characteristics, substance use, and genotype frequencies in 330 men with esophageal cancer and 592 healthy controls. Analyses were adjusted for potential confounders, including baseline variables on which cases and controls significantly differed (e.g., educational attainment, smoking status, alcohol consumption, areca nut chewing).

The odds of esophageal cancer were significantly higher in subjects with

• ADH1B*1/*1 versus ADH1B*2/*2 (odds ratio [OR] 4.0);

• ALDH2*1/*2 or ALDH2*2/*2 versus ALDH2*1/*1 (ORs 5.0 and 4.2, respectively);

• alcohol use, particularly if they had any of the above susceptible genotypes.

Comments:

The results of this study are difficult to interpret. The many baseline differences between groups make it challenging to adequately adjust for confounding in multivariable analysis. Further, the results may be specific to Taiwanese populations. While it is clear that heavy drinking increases the risk of esophageal cancer (as well as cancers of the mouth and pharynx), the specific genetic mechanisms responsible for this risk are still poorly understood.

R. Curtis Ellison, MD

Reference:

Chen YJ, Chen C, Wu DC, et al. Interactive effects of lifetime alcohol consumption and alcohol and aldehyde dehydrogenase polymorphisms on esophageal cancer risks. Int J Cancer. 2006;119(12):2827–2831.