Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms

In this study the GST mu phenotype and ADH genotype at the ADH3 locus were investigated in a group of 39 alcoholic men with upper respiratory/digestive tract cancer: 21 with oropharyngeal cancer and 18 with laryngeal cancer. The results are compared with those of a control group of 37 alcoholic men without alcohol-related medical complications. Of the control subjects, 48% were found to be GST mu deficient [GST mu(-)] and 19% carried the ADH(3)(1)/ADH(3)(1) genotype. In the laryngeal cancer patients, a significantly elevated frequency of both the GST mu(-) (78%) and ADH(3)(1)/ADH(3)(1) genotype (56%) was observed, relative to the control group. On the basis of this result, the risk of laryngeal cancer associated with the GST mu(-) and ADH(3)(1)/ADH(3)(1) genotypic combination within the population of alcoholics was estimated to be 12.9 with a 95% confidence interval of 1.8-92 (P < 0.01) relative to alcoholic individuals who have GST mu [GST mu(+)] and are not ADH(3)(1)/ADH(3)(1). Thus, alcoholics who are GST mu(-) and ADH(3)(1)/ADH(3)(1) have at least an 80% greater risk of developing laryngeal cancer than alcoholics who are GST mu(+) and who are not ADH(3)(1)/ADH(3)(1). In addition, the oropharyngeal cancer patients had excess frequencies of both GSTCL(-) (62%) and ADH(3)(1)/ADH(3)(1) (43%) relative to the control group, but these excess frequencies were not statistically significant. The GST mu(-) and ADH(3)(1)/ADH(3)(1) genotypic combination may be a constitutional risk factor for laryngeal cancer among alcoholics.