Alcohol Dehydrogenase-1B Arg47His Polymorphism and Upper Aerodigestive Tract Cancer Risk: A Meta-Analysis Including 24,252 Subjects

Background: Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus, account for approximately 4% of all new cancers in world. Alcohol drinking is an established risk factor for UADT cancers, and the rate of alcohol metabolism could significantly been influenced by genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) His47Arg (rs1229984). To evaluate whether combined evidence shows ADH1B His47Arg as a common genetic variant that influenced the risk of UADT cancers, we considered all available studies in a meta-analysis. Methods: Eighteen studies were combined representing data of 8,539 cases and 15,713 controls for meta-analysis. Stratified analyses were carried out to determine the gene-environment interaction between ADH1B His47Arg and alcohol drinking and gene-gene interaction between ADH1B His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu/Lys related to UADT cancer risk. Potential sources of heterogeneity between studies were explored; sensitivity analysis and publication bias was also evaluated. Results: The ADH1B 47Arg allele was found to be associated with increased risk of UADT cancers, the pooled odds ratios (ORs) being 1.66 (95% CI: 1.54 to 1.79) and 3.47 (95% CI: 2.76 to 4.36) for the His/Arg and Arg/Arg genotypes compared with the His/His genotype, respectively. An 18.48-fold increase in OR (95% CI: 12.95 to 26.40) for UADT cancers among alcohol drinkers with Arg/Arg genotype was found, when compared among nondrinkers with the His/His genotype. Significant interaction between carriers with ADH1B 47Arg and ALDH2 487Lys allele related to risk for UADT cancers was more evident, compared with noncarriers (OR=10.31, 95% CI: 5.45 to 18.85). Conclusions: ADH1B 47Arg allele is a common genetic variant that increased the risk of UADT cancers; furthermore, it modulates the susceptibility to UADT cancers coupled with alcohol drinking and interaction with the ALDH2 487Lys allele.