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Alcohol consumption interacts with tobacco use to increase the risk of head and neck squamous cell carcinoma (HNSCC). Alcohol is eliminated through oxidation by alcohol dehydrogenase (ADH). The ADH1C gene is polymorphic and the ADH1C*1 allele metabolizes ethanol to acetaldehyde at a higher rate than the variant ADH1C*2 allele. This polymorphism has been reported to alter the risk of HNSCC associated with alcohol use, although the literature differs in the estimates of both the magnitude and direction of this effect modification. We have investigated the association between the established risk factors for HNSCC and variant genotypes of ADH1C in a case-control study in the greater Boston area. ADH1C genotypes were determined from 521 cases and 599 population-based controls. The odds ratio (OR) for HNSCC associated with >26 drinks per week was 3.7 [95% confidence interval (95% CI), 2 …