After adjustment by potential confounders, the significant increase of oral cancer risk, independent of alcohol drinking, was observed in individuals with the variant ADH1C SspI*2/*2 genotype (odds ratio, 3.029; P = .014) and in combined ADH1C SspI*1/*2 and ADH1C SspI*2/*2 genotypes (odds ratio, 2.605; P = .002), compared to the ADH1C*1/1* wild type.
There was a significant interaction of alcohol use and genotype (P = 0.05), with an estimated oral cancer risk in heavy drinkers of 7.1 (95% CI, 2.3-22.0) for homozygous variants compared with an OR of 2.3 (95% CI, 1.4-3.8) for ADH1C homozygous wild type or heterozygous individuals (controlling for smoking, age, race, and gender).
We estimated that OC risk increased by 31.5% per drink/week for the ADH3(2-2) genotype, 4.1% for the ADH3(1-2) genotype and 1.6% for the ADH3(1-1) genotype.
The ADH3(1-1) genotype appears to substantially increase the risk of ethanol-related oral cancer, thus providing further evidence for the carcinogenicity of acetaldehyde.