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

Abstract

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]). 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. 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. 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.