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The Genetic Basis of Alcohol Flushing in Asian Populations

A three-dimensional model of the enzyme that commonly causes alcohol-induced flushing in people of East Asian ancestry. The four colors in the diagram represent four identical protein ribbons stacked across one another to make up ALDH2. Variation in ALDH2 renders it partially inactive, leading to a buildup of toxic acetaldehyde in the body.

Photo courtesy of Thomas Hurley, Ph.D., and colleagues, Indiana University School of Medicine.

You may know someone who flushes bright red after only a few sips of alcohol. This phenomenon, known as alcohol flush, is common among people of East Asian descent and is usually caused by a specific genetic variation that makes an individual unable to fully metabolize, or break down, alcohol in the body.

When you drink, alcohol is first metabolized into acetaldehyde, a toxic byproduct similar to formaldehyde, that causes DNA damage and has other cancer-promoting effects. What looks like a mass of ribbons run amok in the diagram is actually aldehyde dehydrogenase 2 (ALDH2), an enzyme that plays a critical role in breaking down acetaldehyde into acetate, a nontoxic metabolite in the body.

An estimated 30 to 50 percent of people with East Asian ancestry (e.g., Chinese, Japanese, Korean) carry a defect in one or both copies of the ALDH2 gene that codes for the enzyme, causing acetaldehyde to accumulate in the body when they drink alcohol and bringing on facial flushing, as well as nausea and rapid heartbeat for some. The reaction may be more than a nuisance—multiple studies show a strong link between alcohol flush and an increased risk of throat cancer, for example.

Someone with one defective ALDH2 copy may increase his or her risk of esophageal cancer six- to tenfold by consuming just two drinks a day. Based upon these findings, acetaldehyde derived from alcohol metabolism is classified as “carcinogenic to humans” by the International Agency for Research on Cancer. Notably, those with two defective copies of ALDH2 have low rates of alcohol dependence and esophageal cancer because the symptoms of alcohol flushing are so severe they drink very little.

Sources:

Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. The alcohol flushing response: An unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Medicine. 2009 Mar;6(3):e50.

Eng MY, Luczak SE, Wall TL. ALDH2, ADH1B, and ADH1C genotypes in Asians: A literature review. Alcohol Research & Health. 2007;30(1):22-7.

National Institute on Alcohol Abuse and Alcoholism (NIAAA) News Release. Alcohol flush signals increased cancer risk among East Asians. 2009 Mar 23.

World Health Organization; International Agency for Research on Cancer. Personal habits and indoor combustions: Volume 100 E: A review of human carcinogens. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Lyon, France: International Agency for Research on Cancer; 2012;373-499.