Alcohol dehydrogenase 3 genotype is not associated with risk of squamous cell carcinoma of the oral cavity and pharynx

Alcohol is one of the major risk factors for oral and pharyngeal cancer. Th e rate-limiting step in alcohol metabolism is the oxidation (activation) of ethanol to acetaldehyde by the alcohol dehydrogenases (ADHs), It has been hypothesized that individuals who are homozygous for the fast allele (ADH(3 )(1-1)) are at greater risk for alcohol-related cancers. To test this hypot hesis, we investigated the association between the ADH, genotype and oral a nd pharyngeal cancer risk in a large racially homogeneous case-control stud y of 229 patients and 575 matched control subjects with frequency matching on age, sex, and smoking status. Although the smoking status was matched be tween cases and controls, current and former alcohol use remained a signifi cant risk factor, compared with never use (odds ratio, 2.08; 95% confidence interval, 1.37-3.17; odds ratio, 1.97; 95% confidence interval, 1.25-3.09; and odds ratio, 1,00, respectively). The ADH(3)(1) allele frequency of con trols was 57.4%, consistent with reports of similar racial groups (50-60%). The genotype distribution in controls was also consistent with the Hardy-W einberg equilibrium (P = 0,51), However, the ADH(3)(1) allele frequency and ADH(3)(1-1) genotype frequency were not significantly different between ca ses and controls 155.5% versus 57.4% (P = 0,52), and 30.6% versus 31,3% (P = 0,91), respectively]. There was no association between ADH, genotypes (AD H(3)(1-1), ADH(3)(1-2), and ADH(3)(2-2)) and risk of oral and pharyngeal ca ncer (odds ratios, 1.00; 0.96; 95% confidence interval, 0.68-1.37; and odds ratio, 1.23; confidence interval, 0,78-1,93, respectively). Therefore, we found no evidence that supports a main effect of ADH, genotype or a combine d effect of alcohol and ADH, genotype on risk of cancer of the oral cavity or pharynx.