GSTM1 enzyme concentration and enzyme activity in correlation to the genotype of detoxification enzymes in squamous cell carcinoma of the oral cavity

Oral Dis. 2003 Mar;9(2):62-7. doi: 10.1034/j.1601-0825.2003.02866.x.

Abstract

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.

Objectives: 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.

Material and 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.

Conclusion: We assume that detoxification enzymes are functionally redundant and that only the simultaneous deficiency of several detoxification enzymes increases the risk for oral cancer.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Case-Control Studies
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP2D6 / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Glutathione Transferase / analysis
  • Glutathione Transferase / genetics*
  • Glutathione Transferase / metabolism*
  • Humans
  • Inactivation, Metabolic / genetics*
  • Male
  • Middle Aged
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Statistics, Nonparametric

Substances

  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2D6
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1