Alcohol consumption increases the likelihood of several other disorders. For example, population-based studies have demonstrated that esophageal cancer is linked to alcohol consumption as a result of the tissue’s exposure to ethanol and its metabolite acetaldehyde. Consequently, functional variants in ADH1B and ALDH2 that affect alcohol clearance and acetaldehyde accumulation also play a role in the development of esophageal cancer. The effects of these variants on cancer are strongly moderated by accompanying alcohol exposure. For example, people who carry the ADH1B*2 allele that results in more rapid ethanol conversion to acetaldehyde, experience flushing and, hence, have reduced likelihood of alcohol intake, protecting them from esophageal cancer. Conversely, people who carry the ADH1B*1 variant, which results in slower alcohol metabolism, are at increased risk for esophageal cancer, arguably because of extended tissue exposure to ethanol. Likewise, having the ALDH2*2 allele, which inactivates aldehyde dehydrogenase, has protective effects on both alcohol intake and esophageal cancer. However, people who carry only one copy of ALDH2*2 often continue to drink, which leads to acetaldehyde accumulation and consequently increases the risk for esophageal cancer (Brooks et al. 2009).
