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

Abstract

In this study the GSTμ 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 GSTμ deficient [GSTμ(–)] and 19% carried the ADH₃ ¹/ADH₃ ¹ genotype. In the laryngeal cancer patients, a significantly elevated frequency of both the GSTμ(–) (78%) and ADH₃ ¹/ADH₃ ¹ genotype (56%) was observed, relative to the control group. On the basis of this result, the risk of laryngeal cancer associated with the GSTμ(–) and ADH₃ ¹/ ADH₃ 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 GSTμ [GSTμ(+)] and are not ADH₃ ¹/ADH₃ ¹. Thus, alcoholics who are GSTμ(–) and ADH₃ ¹/ADH₃ ¹ have at least an 80% greater risk of developing laryngeal cancer than alcoholics who are GSTμ(+) and who are not ADH₃ ¹/ ADH₃ ¹. In addition, the oropharyngeal cancer patients had excess frequencies of both GSTμ(–) (62%) and ADH₃ ¹/ ADH₃ ¹ (43%) relative to the control group, but these excess frequencies were not statistically significant. The GSTμ(–) and ADH₃ ¹/ADH₃ ¹ genotypic combination may be a constitutional risk factor for laryngeal cancer among alcoholics.