Gene polymorphisms in detoxification enzymes as susceptibility factor for head and neck cancer?

Otolaryngol Head Neck Surg. 2003 May;128(5):674-80. doi: 10.1016/S0194-59980300176-1.

Abstract

Objective: Impaired detoxification of carcinogens found in tobacco smoke appears to increase the risk for tobacco associated cancer. The objective of this study was to investigate concomitant polymorphisms in genes encoding for various detoxification enzymes in patients with head and neck squamous cell carcinoma (HNSCC).

Methods: In 187 patients with HNSCC and in 139 healthy control subjects, the polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2D6 (CYP2D6), and glutathione S-transferase mu1 and Theta (GSTM1, GSTT1) were detected by polymerase chain reaction.

Results: No significant association were identified between CYP1A1 and CYP2D6 gene polymorphisms and HNSCC. Patients with laryngeal cancer revealed the GSTM1 null genotype more frequently than did the control subjects (P < 0.05). The coincidence of GSTM1 and GSTT1 null genotype was found twice as great in patients as in control subjects (P < 0.05).

Conclusions: It is assumed that detoxification enzymes are functionally redundant and only the simultaneous deficiency of several detoxification enzymes increase the risk for HNSCC in alcohol- and tobacco-exposed individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alcohol-Related Disorders / genetics
  • Alcohol-Related Disorders / metabolism
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics*
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Glutathione Transferase / genetics*
  • Glutathione Transferase / metabolism
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Inactivation, Metabolic / genetics*
  • Inactivation, Metabolic / physiology
  • Male
  • Middle Aged
  • Polymorphism, Genetic / physiology*
  • Tobacco Use Disorder / genetics
  • Tobacco Use Disorder / metabolism

Substances

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