C. Coutelle et al., LARYNGEAL AND OROPHARYNGEAL CANCER, AND ALCOHOL-DEHYDROGENASE-3 AND GLUTATHIONE-S-TRANSFERASE M1 POLYMORPHISMS, Human genetics, 99(3), 1997, pp. 319-325
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 respirator
y/digestive tract cancer: 21 with oropharyngeal cancer and 18 with lar
yngeal 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 c
ancer 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 laryng
eal cancer associated with the GST mu(-) and ADH(3)(1)/ADH(3)(1) genot
ypic 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 t
o 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 t
han 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 c
ontrol group, but these excess frequencies were not statistically sign
ificant. The GST mu(-) and ADH(3)(1)/ADH(3)(1) genotypic combination m
ay be a constitutional risk factor for laryngeal cancer among alcoholi
cs.