Journal Article

Genetic polymorphisms in UDP-glucuronosyltransferases and glutathione <i>S</i>-transferases and colorectal cancer risk

E.M.J. van der Logt, S.M. Bergevoet, H.M.J. Roelofs, Z. van Hooijdonk, R.H.M. te Morsche, T. Wobbes, J.B. de Kok, F.M. Nagengast and W.H.M. Peters

in Carcinogenesis

Volume 25, issue 12, pages 2407-2415
Published in print December 2004 | ISSN: 0143-3334
Published online December 2004 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgh251
Genetic polymorphisms in UDP-glucuronosyltransferases and glutathione S-transferases and colorectal cancer risk

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Colorectal cancer (CRC) is one of the most common malignancies in the Western world showing an increasing incidence, and has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. To determine whether genetic polymorphisms in detoxification enzymes predispose to the development of CRC, 371 patients with sporadic CRC and 415 healthy controls were genotyped for polymorphisms in the important detoxification enzymes UDP-glucuronosyltransferase UGT1A1, UGT1A6, UGT1A7 and UGT1A8, and glutathione S-transferase GSTA1, GSTM1, GSTP1 and GSTT1. Patients and controls were all of Caucasian origin. DNA was isolated from either blood or tissue and tested by polymerase chain reaction followed by restriction fragment length polymorphism analyses. Logistic regression analyses showed significant age- and gender-adjusted risks for CRC associated with variant genotypes of UGT1A6 [OR 1.5, 95% (confidence interval) CI 1.03–2.3] and UGT1A7 (OR 2.4, 95% CI 1.3–4.6), whereas no associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, the data suggest that the presence of variant UGT1A6 and UGT1A7 genotypes with expected reduced enzyme activities, might enhance susceptibility to CRC.

Keywords: CI, confidence interval; CRC, colorectal cancer; HCA, heterocyclic amines; ITC, isothiocyanates; RFLP, fragment length polymorphism; UGT, UDP-glucuronosyltransferase

Journal Article.  7628 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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