Alcohol consumed by ALDH2-deficient individuals is metabolized to acetaldehyde, which accumulates in the body due to absent ALDH2 activity and results in facial flushing (Figure 1), nausea, and tachycardia [2]. These unpleasant effects are the result of diverse actions of acetaldehyde in the body, including histamine release [10]. Because of the intensity of this unpleasant response, ALDH2 Lys/Lys homozygotes are unable to consume significant amounts of alcohol. As a result, they are protected against the increased risk of esophageal cancer from alcohol consumption [11]. This observation also provided evidence for a causative role for ethanol in esophageal cancer, and a key role for acetaldehyde in mediating this effect [11].
