Cytochrome P450: Polymorphisms and Roles in Cancer, Diabetes and Atherosclerosis

Abstract

Cytochromes P450s (CYPs) constitute a superfamily of enzymes that catalyze the metabolism of drugs and other<br />substances. Endogenous substrates of CYPs include eicosanoids, estradiol, arachidonic acids, cholesterol, vitamin D<br />and neurotransmitters. Exogenous substrates of CYPs include the polycyclic aromatic hydrocarbons and about 80% of<br />currently used drugs. Some isoforms can activate procarcinogens to ultimate carcinogens. Genetic polymorphisms of<br />CYPs may affect the enzyme catalytic activity and have been reported among different populations to be associated<br />with various diseases and adverse drug reactions. With regard of drug metabolism, phenotypes for CYP polymorphism<br />range from ultrarapid to poor metabolizers. In this review, we discuss some of the most clinically important CYPs<br />isoforms (CYP2D6, CYP2A6, CYP2C19, CYP2C9, CYP1B1 and CYP1A2) with respect to gene polymorphisms and<br />drug metabolism. Moreover, we review the role of CYPs in renal, lung, breast and prostate cancers and also discuss<br />their significance for atherosclerosis and type 2 diabetes mellitus.