CYP2E1 and risk of chemically mediated cancers.
BACKGROUND
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.


METHODS
Literature searches of MEDLINE (1966 to July 2009) for English articles in CYP2E1-induced carcinogenesis were conducted.


RESULTS
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.


CONCLUSIONS
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.
Trafalis
Dimitrios T
DT
Department of Pharmacology, University of Athens Medical School, 75 Mikras Asias Street, Athens, Greece.
Panteli
Eleftheria S
ES
Grivas
Anastasios
A
Tsigris
Christos
C
Karamanakos
Petros N
PN
D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity
D002273:Carcinogens; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D015262:Xenobiotics; D019392:Cytochrome P-450 CYP2E1