Variants in ADH1B and ALDH2 that influence alcohol consumption and alcohol dependence also play a role in the risk for upper aero-digestive tract (UADT) cancer. The protein encoded by the ADH1B*2 allele, which is associated with reduced risk for alcohol dependence, has increased enzyme activity. Protein encoded by the ALDH2*2 allele, a protective allele for alcohol dependence, has almost zero enzyme activity (33). Individuals who carry these two alleles have much higher levels of acetaldehyde (a carcinogen) compared with noncarriers if they consume alcohol (Figure 2). Studies have shown that, owing to the accumulation of acetaldehyde in the blood, individuals who have the alcohol flushing response are at higher risk for esophageal cancer (21).
