CYP2E1 and risk of chemically mediated cancers

Expert Opin Drug Metab Toxicol. 2010 Mar;6(3):307-19. doi: 10.1517/17425250903540238.

Abstract

Importance of the field: Among various human CYPs, CYP2E1 is of particular interest because of its involvement in the metabolic activation of many low molecular mass procarcinogens. CYP2E1 induction, which may be a consequence of genetic polymorphism or/and gene induction by xenobiotics, is the first step leading to the development of certain chemically-mediated cancers. The aim of this review is to outline the current knowledge on chemically-induced cancers through activation by CYP2E1, with emphasis on the association between polymorphisms of the CYP2E1 gene and incidence of different neoplasias.

Areas covered in this review: Literature searches of MEDLINE (1966 to July 2009) for English articles in CYP2E1-induced carcinogenesis were conducted.

What the reader will gain: CYP2E1 genetic polymorphisms leading to enhanced CYP2E1 gene transcription have been associated with increased risk of development of malignant tumours, through increased biotransformation of procarcinogens. Likewise, long-term intake of CYP2E1 inducers, such as ethanol, isoniazid, various solvents and chemicals, also increase the probability of developing malignancy, especially for carriers of certain CYP2E1 alleles.

Take home message: Genetic screening for CYP2E1 'carcinogenic' polymorphisms and CYP2E1 phenotype determination of susceptible subjects, as well as the development of effective CYP2E1 inhibitors, could be a future perspective towards prevention of CYP2E1-mediated cancers.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogens / metabolism
  • Carcinogens / pharmacology
  • Carcinogens / toxicity
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Cytochrome P-450 CYP2E1 Inhibitors
  • Enzyme Induction / drug effects
  • Enzyme Induction / genetics
  • Humans
  • Neoplasms / chemically induced*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Xenobiotics / metabolism*
  • Xenobiotics / pharmacology*
  • Xenobiotics / toxicity

Substances

  • Carcinogens
  • Cytochrome P-450 CYP2E1 Inhibitors
  • Xenobiotics
  • Cytochrome P-450 CYP2E1