In several of these studies, the effects of ADH1B and ALDH2 variants predominantly were noted in those who drink alcohol. For instance, even in people with two copies of the ALDH2*2 allele, which is highly protective for alcohol intake, the few drinkers are at a profoundly elevated risk for esophageal cancer (Yang et al. 2010). It might be hypothesized that this finding reflects a genotype–environment correlation where ALDH2 and ADH1B variants influence the likelihood of continued alcohol (and acetaldehyde) exposure, which, in turn, serves as the environmental risk factor for the development of esophageal cancer, either as a result of prolonged ethanol exposure or of the carcinogenic effects of acetaldehyde. An alternative explanation is that of a genotype × environment interaction—that is, people who carry the ALDH2 and ADH1B genotypes that protect against alcohol intake might be exquisitely sensitive to the joint effects of genotype and alcohol consumption on their vulnerability to esophageal cancer.
