Objectives: Alcohol increases esophageal squamous carcinoma risk but has been less consistently associated with esophageal adenocarcinoma. Alcohol dehydrogenase catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a carcinogen. The alcohol dehydrogenase gene has several polymorphisms which may lead to faster conversion of ethanol to acetaldehyde, which may increase cancer risk.
Methods: We undertook a study to examine whether a common polymorphism in the alcohol dehydrogenase 3 gene was associated with a higher risk of esophageal adenocarcinoma using data and biological samples collected for the Esophageal and Gastric Cancer Study (n = 114 esophageal and gastric cardia adenocarcinoma, n = 60 non-cardia gastric carcinoma, n = 23 cases of esophageal squamous cell carcinoma and 160 controls).
Results: Individuals homozygous for ADH ( 3 ) (1-1) had a higher risk of each tumor type compared to individuals who had ADH ( 3 ) (2-2) or ADH ( 3 ) (1-2) genotype (OR = 1.7, 95% CI = 1.0-2.9 for esophageal and gastric cardia adenocarcinomas; OR = 1.7, 95% CI = 0.7-4.3 for esophageal squamous cell carcinoma; and OR = 2.8, 95% CI = 1.5-5.1 for non-cardia gastric cancer). The elevation in risk from homozygosity of the ADH ( 3 ) (1) allele was seen in drinkers and nondrinkers, although the risk estimate was only significant for drinkers, particularly of liquor.
Conclusion: These data suggest ADH3 genotype may be associated with risk of esophageal and gastric cardia adenocarcinomas.