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Altered Gene Puts Asians at Higher Risk of Esophageal Cancer


For many Asian people, drinking alcohol can be unpleasant. That's because alcohol causes them to feel nauseated and to experience a flushed, red face. Now researchers in Japan and the United States are finding that those same people are at higher risk of developing cancer of the esophagus.

Many East Asians carry a common genetic variation that creates a deficiency in the production of an enzyme called aldehyde dehydrogenase 2, or ALDH2. It's this gene that causes their faces to become very red - or flushed - when they drink.

Researcher Philip Brooks from the U.S. National Institute of Alcohol Abuse and Alcoholism explains that when a person who's deficient in ALDH2 drinks alcohol, it's first metabolized to another chemical called acetaldehyde.

"That's the first metabolite of the alcohol," Brooks says. "That acetaldehyde is then normally metabolized to another chemical that's basically harmless. So individuals with the ALDH2 deficiency can't metabolize the acetaldehyde into this non-toxic chemical. So the acetaldehyde builds up in their blood, and it's the build-up of that acetaldehyde that causes them to get the red face and the flushing and the nausea."

Brooks worked with Japanese researcher Akira Yokoyama, who's been looking at the problem for a long time. Together, examined data from Japan and Korea, where many people have this ALDH2 deficiency. One problem in these countries is that despite the physical discomfort of facial flushing and nausea, many of them still drink large quantities of alcohol.

Brooks says they've found that these drinkers end up developing a form of esophageal cancer at rates six to 10 times greater than for people who don't have the altered gene.

"In general, esophageal cancer is very deadly," Brooks says. "The five-year survival rate is … between 12 and maybe 30 percent." Brooks and Yokoyama found that the more a person with ALDH2 deficiency drank, the higher their chances of developing this deadly esophageal cancer. Brooks explains that knowing about this increased facial flushing could be valuable to doctors.

"If they [doctors] have a patient of East Asian descent, and they want to know if they are ALDH2 deficient, they basically just have to ask them a couple of questions about their experience with alcohol and flushing," Brooks says. "And that doesn't cost anything... That's free."

Brooks says the main goal of publishing this paper is to get doctors talking to their patients with the ALDH2 deficiency about limiting their intake of alcohol. Brooks and Yokoyama's paper is published in the journal PLoS Medicine.

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