Enzyme needed to degrade acetaldehyde

When a person drinks alcohol, two different enzymes in the liver break it down, first into acetaldehyde and then into acetate. People with a shortage of the second enzyme, aldehyde dehydrogenase-2 (ALDH-2)—which is normally detected in blood and saliva—can’t break down acetaldehyde efficiently. This compound accumulates in their saliva, European researchers report in the June Alcoholism: Clinical And Experimental Research.

Excess acetaldehyde in the mouth may explain why alcoholics lacking ALDH-2 have such high rates of cancer of the mouth, throat, and stomach, says study coauthor Mikko Salaspuro of Helsinki University Central Hospital.

Animal and cell-culture studies have linked acetaldehyde to cancer. “In our human studies, we have obtained a lot of indirect evidence about the possible local carcinogenic action of acetaldehyde,” he says. Heavy drinking, smoking, and poor oral hygiene, which all boost salivary acetaldehyde concentrations, heighten the risk of mouth and throat cancers, he says.

Among Asians, 2 percent of people carry a genetic mutation that causes them to totally lack ALDH-2. In nearly all cases, these people can’t drink alcohol because it makes them flushed, dizzy, and nauseated.

Many other Asians, including nearly half of the Japanese population, have a milder form of the mutation. These people produce some ALDH-2 but typically less than one-third the normal amount. They have less severe reactions to alcohol than people without any ALDH-2. These milder symptoms deter most people from drinking, but not all, Salaspuro says. Studies show that 8 to 10 percent of Japanese alcoholics are partially ALDH-2 deficient.

The researchers compared 7 healthy Asian volunteers who had the mild ALDH-2 deficiency with 13 Asians who had normal ALDH-2 concentrations. After giving each volunteer a standard-size alcoholic drink, the scientists found that saliva in the ALDH-2-deficient group contained two to three times as much acetaldehyde as the other group’s saliva did.

If further tests verify these findings, the mutation causing ALDH-2 deficiency may prove to be a key risk factor for cancer, Salaspuro concludes. While heavy drinkers worldwide have a high risk of esophageal cancer, Asian alcoholics also have a high risk of other digestive-tract cancers. This could be attributable to ALDH-2 deficiency in Asians, Salaspuro hypothesizes.

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