Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer

Abstract

In humans, the liver is generally considered to be the major organ contributing to drug metabolism, but studies during the last years have suggested an important role of the extra-hepatic drug metabolism. The gastrointestinal tract (GI-tract) is the major path of entry for a wide variety of compounds including food, and orally administered drugs, but also compounds – with neither nutrient nor other functional value – such as carcinogens. These compounds are metabolized by a large number of enzymes, including the cytochrome P450 (CYP), the glutathione S-transferase (GST) family, the uridine 5′-diphospho- glucuronosyltransferase (UDP-glucuronosyltransferase – UGT) superfamily, alcohol-metabolizing enzymes, sulfotransferases, etc. These enzymes can either inactivate carcinogens or, in some cases, generate reactive species with higher reactivity compared to the original compound. Most data in this field of research originate from animal or in vitro studies, wherein human studies are limited. Here, we review the human studies, in particular the studies on the phenotypic expression of these enzymes in the colon and rectum to get an impression of the actual enzyme levels in this primary organ of exposure. The aim of this review is to give a summary of currently available data on the relation between the CYP, the GST and the UGT biotransformation system and colorectal cancer obtained from clinical and epidemiological studies in humans.

• Biotransformation
• colorectal cancer
• cytochrome P450
• glutathione S-transferase
• UDP-glucuronosyltransferase

Acknowledgements

We thank Robert Wyn Owen for proofreading and editing the manuscript.

Declaration of interest

The authors report no declarations of interest. This study was financially supported by the Department of Preventive Oncology, German Cancer Research Center.