Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms.
In this study the GSTmu 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 GSTmu deficient [GSTmu(-)] and 19% carried the ADH(3)1/ADH(3)1 genotype. In the laryngeal cancer patients, a significantly elevated frequency of both the GSTmu(-) (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 GSTmu(-) 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 GSTmu [GSTmu(+)] and are not ADH(3)1/ADH(3)1. Thus, alcoholics who are GSTmu(-) and ADH(3)1/ADH(3)1 have at least an 80% greater risk of developing laryngeal cancer than alcoholics who are GSTmu(+) and who are not ADH(3)1/ADH(3)1. In addition, the oropharyngeal cancer patients had excess frequencies of both GSTmu(-) (62%) and ADH(3)1/ADH(3)1 (43%) relative to the control group, but these excess frequencies were not statistically significant. The GSTmu(-) and ADH(3)1/ADH(3)1 genotypic combination may be a constitutional risk factor for laryngeal cancer among alcoholics.
Coutelle
C
C
Université de Bordeaux II, France. christiane.coutelle@dbm2.u-bordeaux2.fr
Ward
P J
PJ
Fleury
B
B
Quattrocchi
P
P
Chambrin
H
H
Iron
A
A
Couzigou
P
P
Cassaigne
A
A
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000150:complications; D016022:Case-Control Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D012307:Risk Factors
D000426:Alcohol Dehydrogenase; D005982:Glutathione Transferase