The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption

A Primer on the Genetics of Alcohol MetabolismEthanol is first metabolized primarily by alcohol dehydrogenase (ADH) into acetaldehyde (Figure 2), a mutagen and animal carcinogen that causes DNA damage and has other cancerpromoting effects [5][6][7].Acetaldehyde is subsequently metabolized to acetate, mainly by the enzyme ALDH2 [8].In East Asian populations there are two main variants of ALDH2, resulting from the replacement of glutamate (Glu) at position 487 with lysine (Lys) [9].The Glu allele (also designated ALDH2*1) encodes a protein with normal catalytic activity, whereas the Lys allele (ALDH2*2) encodes an inactive protein.As a result, Lys/ Lys homozygotes have no detectable Funding: The authors received no specific funding for this article.