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Genetic Polymorphisms of Drug Metabolising Enzymes and Drug Transporters in Relation to Cancer Risk

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Abstract:

There is a wide variation in cancer incidence in humans, which, in part, has been attributed to metabolic factors of carcinogens and genetic polymorphisms in drug metabolising enzymes and drug transporters. Drug metabolising enzymes are responsible for the initial activation of many (pro)carcinogens, such as polycyclic aromatic hydrocarbons (PAH), to biologically reactive metabolites. Besides, detoxifying enzymes are responsible for the inactivation of these active carcinogens and deficiency of these enzymes may result in an increase of cancer risk in exposed individuals. Another factor influencing interindividual variability in cancer incidence is the transporters, which are responsible for the excretion of carcinogens. A high number of polymorphisms have been described in drug metabolising enzymes and drug transporter genes. These polymorphisms might influence the activity of metabolising enzymes and drug transporters and thereby affect cancer risk. This review will focus on the role of genetic polymorphisms of selected drug metabolising enzymes (CYP1A1, 2C9, 2C19, 3A4, 3A5, UGT1A1, GSTM1, GSTP1, GSTT1, SULT1A1, NAT1 and NAT2) and ABCtransporters (P-gp and BRCP) in relation to cancer risk.





Keywords: Polymorphisms; cancer risk; drug transporters; drug-metabolising enzymes

Document Type: Research Article

DOI: https://doi.org/10.2174/157339406776872825

Affiliations: Louwesweg 6, 1066 EC Amsterdam, The Netherlands.

Publication date: 2006-05-01

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  • Current Cancer Therapy Reviews publishes frontier reviews on all the latest advances in clinical oncology, cancer therapy and pharmacology. The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians in cancer therapy.
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