UGT1A1 polymorphisms and colorectal cancer susceptibility
- Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen AB25 2ZD, UK; n.t.brockton@abdn.ac.uk
UDP-glucuronosyltransferase (UGT) 1A7 polymorphisms may be involved in the aetiology of colorectal cancer
The contribution of the xenobiotic metabolising enzymes (XMEs) to disease susceptibility, particularly cancer, has been a focus for a great deal of research over the last two decades.1 Many of these genes are polymorphic and exhibit significant interindividual variation in their activity. Although these enzymes all have endogenous substrates, they are also involved in the metabolism of exogenous, often mutagenic, substances to which humans are exposed.2
The central hypothesis of these studies has been that genetic changes functionally alter the enzymes and consequently modify an individual's response to a given exposure, putatively associated with the disease. The increased risk for the individual is likely to be small. However, the higher frequency of these alterations, compared with the risks associated with genetic defects implicated in familial syndromes, raises the possibility that the attributable risk, at the population level, may be substantial and therefore of considerable public health importance.3
The involvement of UDP-glucuronosyltransferase (UGT) 1A7 polymorphisms in the aetiology of colorectal cancer (CRC) is presented by Strassburg et al in this issue of Gut4[see page 851] is biologically plausible. The authors have shown that …
