CYP2E1 and risk of chemically mediated cancers.

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.

• Authors: Dimitrios T Trafalis, Eleftheria S Panteli, Anastasios Grivas, Christos Tsigris, Petros N Karamanakos
• Journal: Expert opinion on drug metabolism & toxicology (Expert Opin Drug Metab Toxicol) Vol. 6 Issue 3 Pg. 307-19 (Mar 2010) ISSN: 1744-7607 [Electronic] England
• PMID: 20073996 (Publication Type: Journal Article, Review)

Chemical References

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

Topics

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