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

Document Type: Systematic Review and Meta-analysis

Authors

1 Department of Biochemistry, Faculty of Science, University of Tabuk, Kingdom of Saudi Arabia.

2 Prince Fahd Ben Sultan Research Chair, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Kingdom of Saudi Arabia.

Abstract

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

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