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

Tessa   M.   Bosch; Irma      Meijerman; Jos   H.   Beijnen; Jan   H.M.   Schellens

doi:10.2174/157339406776872825

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, drug-metabolising enzymes, drug transporters, cancer risk

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