GSTM1 enzyme concentration and enzyme activity in correlation to the genotype of detoxification enzymes in squamous cell carcinoma of the oral cavity.
BACKGROUND
Differences in genotype and phenotype of detoxification genes could be one reason for conflicting results in studies dealing with gene polymorphisms as susceptibility factors for tobacco associated cancer.


OBJECTIVE
The objective of this study was to investigate gene polymorphisms of detoxification enzymes and to determine whether the enzyme concentration and activity of glutathione S transferase microliter 1 correlates with the genotype in patients with cancer of the oral cavity.


METHODS
In 73 cancer patients and 136 matched healthy controls, the polymorphisms of glutathione S-transferase mu1 and theta (GSTM/GSTT), cytochrome p450 1A1 and CYP2D6 were detected. Simultaneously, GSTM1 protein concentration and total GSTM1-activity were determined.


RESULTS
Only the coincidence of GSTM1 and GSTT null genotype was associated with oral cavity cancer. GSTM1 protein concentration and enzyme activity in null-genotype patients was significantly lower than in GSTM1-allele-carrier. But the enzyme concentration did not correlate with the activity.


CONCLUSIONS
We assume that detoxification enzymes are functionally redundant and that only the simultaneous deficiency of several detoxification enzymes increases the risk for oral cancer.
Gronau
S
S
Department of Otorhinolaryngology, University Ulm, Germany.
Koenig-Greger
D
D
Jerg
M
M
Riechelmann
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018709:Statistics, Nonparametric
D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1