Plethoric topers beware

The NY Times has an article about a study suggesting people who drink a lot and get red in the face when they do it may have a high risk of esophageal cancer.
Many people get flushed when they drink alcohol because of general dermal vasodilaton, but this article concerns a special class of people who are deficient in the enzyme ALDH2, or aldehyde dehydrogenase. Normally, ethyl alcohol is broken down into carbon dioxide and water in a series of oxidation reactions: ethanol –> acetaldeyde –> acetic acid –> CO2 and H2O. ALDH2 is responsible for the second step in this chain, meaning that people who lack it altogether experience a build-up of acetaldehyde in their bodies, with extremely unpleasant results. In fact, the drug disulfiram (Antabuse), sometimes given as a drinking deterrent, acts by inhibiting ALDH2 activity. (Side note: in the case of methanol poisoning, ALDH2 oxidizes formaldehyde into formic acid, an extremely retinotoxic substance. This is why people who mistakenly drank “wood alcohol” in days of yore would often go blind a couple of days later.)
Many East Asians are affected by this enzyme deficiency. People who are homozygous for it have a lifelong, built-in “Anatbuse reaction” and can never drink. Heterozygotes, on the other hand, can eventually reach levels of chronic consumption rivaling any other imbiber’s, and these are people mentioned in the article as being at risk for esophageal CA.

The malignancy, called squamous cell esophageal cancer, is also caused by smoking and can be treated with surgery, but survival rates are very low. Even moderate drinking increases the risk, but it rises sharply with heavier consumption. An ALDH2-deficient person who has two beers a day has six to 10 times the risk of developing esophageal cancer as a person not deficient in the enzyme.

It’s not clear from the article whether the mechanism for the increased risk among ALDH2 people has been elucidated, but my guess is that it hasn’t.