Epistasis of oxidative stress-related enzyme genes on modulating the risks in oral cavity cancer

Clin Chim Acta. 2010 Nov 11;411(21-22):1705-10. doi: 10.1016/j.cca.2010.07.007. Epub 2010 Jul 17.

Abstract

Background: The aim of this study was to evaluate the risks of the polymorphisms of oxidant stress-related enzymes on patients with oral cavity cancer by genotyping of manganese superoxide dismutase (MnSOD [1183T>C]), myeloperoxidase (MPO [-463G>A]), catalase (CAT [-15A>T]) and glutathione peroxidases 1 (GPx1 [Pro198Leu]).

Methods: A case-control study was conducted on 122 biopsy-proven oral cavity cancer patients with, at least, one of the past habits of cigarette smoking, alcohol drinking or betel-quid chewing, and 122 approximately age- and habit-matched controls.

Results: The independent risks of the polymorphisms for each enzyme on carcinogenicity were non-significant. The 2-order gene-gene interactions of the polymorphisms, assessed by using a logistic regression model, on risk did not show significant changes, neither. However, the epistasis, assessed by multifactor dimensionality reduction (MDR) for three-order (CAT, MnSOD, and MPO) and four-order was significant. Additionally, the fact that the levels of O(2)(-), GSSG and total GSH in the patients were significantly different according to certain genotypes which revealed that the polymorphisms of these enzymes could affect these parameters to some extent.

Conclusions: The results suggested that the genetic-effects of the polymorphisms of these enzymes could slightly modify the risk in oral cavity cancer development individually, but significantly when they functioned together.

MeSH terms

  • Adult
  • Case-Control Studies
  • Catalase / genetics
  • Epistasis, Genetic*
  • Genotype
  • Glutathione / genetics
  • Humans
  • Middle Aged
  • Mouth Neoplasms / etiology
  • Mouth Neoplasms / genetics*
  • Oxidative Stress / genetics*
  • Oxidoreductases / genetics*
  • Peroxidase / genetics
  • Peroxidases / genetics
  • Polymorphism, Genetic
  • Risk
  • Substance-Related Disorders
  • Superoxide Dismutase / genetics

Substances

  • Oxidoreductases
  • Peroxidases
  • Catalase
  • Peroxidase
  • Superoxide Dismutase
  • Glutathione