Genotype and phenotype of glutathione-S-transferase in patients with head and neck carcinoma.
OBJECTIVE
Association of glutathione-S-transferase M1 (GSTM1) polymorphisms and cancer has been demonstrated. Possible underlying mechanisms and genotype-phenotype correlations are not adequately investigated. The aim of this study was to investigate the influence of the GSTM1-null-genotype on the level of GSTM enzyme concentration and on the enzyme activity of GST in patients with head and neck cancer (HNC).


METHODS
We investigated in 83 patients and 91 healthy controls the GSTM1 polymorphisms, GSTM1 protein concentration, GSTM1 protein in tumor tissues, and total GST enzyme activity.


RESULTS
Total GST enzyme activity was significantly lower in patients with HNC (208 +/- 9 micromol/min*l) than in controls (264 +/- 11 micromol/min*l, P< 0.0001) but did not depend on GSTM1-genotype (P = 0.1). GSTM protein concentration in null-genotype patients (3.6 +/- 2.5 microg/mL, mean +/- SE) was significantly lower than in GSTM1 allele carriers (26.7 +/- 9.6 microg/ml, P< 0.0001); GSTM protein expression did not depend on GSTM1-genotype (P> 0.5).


CONCLUSIONS
GST enzyme activity in patients with HNC is suppressed, indicating impaired detoxification capacity of tobacco-smoke-related carcinogens. This suppression is not correlated with the GSTM1-genotype.
Konig-Greger
Diemut
D
Department of Otorhinolaryngology, Institute of Clinical Chemistry, University of Ulm, Germany.
Riechelmann
Herbert
H
Wittich
Uta
U
Gronau
Silke
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012907:Smoking
D005982:Glutathione Transferase