Many people of East Asian descent possess an enzyme deficiency that causes their skin to redden, or flush, when they drink alcohol.   Scientists from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and Japan's KurihamaAlcoholCenter now caution that heavy alcohol consumption greatly increases the risk for esophageal cancer among such individuals, who comprise about 8 percent of the world's population. Their review of recent research on this topic appears in the March 24, 2009 issue of PLoS Medicine.   NIAAA is part of the National Institutes of Health.

"It is very important for clinicians who treat patients of East Asian descent to be aware of the risk of esophageal cancer from alcohol consumption in their patients who exhibit the alcohol flushing response, so they can counsel them about limiting their drinking," says NIAAA Acting Director Kenneth R. Warren, Ph.D.

First author Philip J. Brooks, Ph.D., of NIAAA's Laboratory of Neurogenetics, and his colleagues note that a clinician can reliably determine whether a patient is at risk simply by asking about previous episodes of facial flushing after drinking alcohol.   Considered from this perspective, the authors point out, the flushing response is a clinically useful biomarker of genetic susceptibility to esophageal cancer risk from alcohol.

Dr. Brooks cites the high mortality from esophageal cancer and the large number of individuals with the deficient enzyme, known as aldehyde dehydrogenase 2 (ALDH2).

"Cancer of the esophagus is particularly deadly, with five-year survival rates ranging from 12 to 31 percent throughout the world.   And we estimate that at least 540 million people have this alcohol-related increased risk for esophageal cancer," he notes.   "We hope that, by raising awareness of this important public health problem, affected individuals who drink will reduce their cancer risk by limiting their alcohol consumption."

Dr. Brooks and his colleagues explain that ALDH2 plays an important role in alcohol metabolism. When alcohol is consumed, it is first metabolized into acetaldehyde, a chemical similar to formaldehyde, which causes DNA damage and has other cancer-promoting effects.   ALDH2 is the main enzyme responsible for breaking down acetaldehyde into acetate, a non-toxic metabolite in the body.

East Asians have two main variants of the ALDH2 gene -- one that produces an enzyme with normal activity, and another that results in an inactive enzyme. When individuals with the inactive variant drink alcohol, acetaldehyde accumulates in the body, resulting in facial flushing, nausea, and rapid heartbeat.   For people with two copies of the inactive variant, these symptoms are so severe that they can drink very little alcohol. However, individuals with only one copy of the inactive variant can become tolerant to the unpleasant effects of acetaldehyde, which puts them at risk for alcohol-related esophageal cancer.

A series of epidemiologic studies by Akira Yokoyama and his colleagues in Japan have shown that individuals with one copy of the inactive variant are about 6-10 times more likely to develop esophageal cancer than are individuals with the fully active ALDH2 enzyme who drink comparable amounts of alcohol.   Notably, these studies showed that individuals with the inactive variant who drink the equivalent of 33 or more U.S. standard drinks per week have a 89-fold increased risk of esophageal cancer compared to non-drinkers.   Dr. Yokoyama is a co-author of the latest report.

The researchers add that many ALDH2-deficient university students may have their first experiences with heavy drinking while in college. Therefore, it is particularly important for university health professionals to be aware of the relationship between ALDH2-deficiency, facial flushing, and alcohol-related cancer risk. Informing ALDH2-deficient young people of their risk of esophageal cancer from alcohol drinking represents a valuable and cost-effective opportunity for cancer prevention.