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DNA mismatch repair status may influence anti-neoplastic effects of butyrate

Lookup NU author(s): Dr Jonathan Coxhead, Dr Liz Williams, Professor John Mathers

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Abstract

HNPCC (hereditary non-polyposis colon cancer) is an autosomal-dominant disorder characterized by early-onset CRC (colorectal cancer). HNPCC is most often associated with mutations in the MMR (mismatch repair) genes hMLH1, hMSH2, hMSH6 or hPM52. The mutator phenotype of a defective MMR system is MSI (microsatellite instability), which also occurs in approx. 15-25% of sporadic CRC cases, where it is associated with the hypermethylation of the promoter region of hMLH1. Dietary factors, including excessive alcohol consumption, ingestion of red meat and low folate intake, may increase the risk of MSI high tumour development. In contrast, aspirin may suppress MSI in MMR-deficient CRC cell lines. Butyrate, a short-chain-fatty-acid end product of carbohydrate fermentation in the colon, shares a number of anti-neoplastic properties with aspirin, including inhibiting proliferation and inducing apoptosis of CRC cells. Recent in vitro studies suggest that physiological concentrations of butyrate (0.5-2 mM) may have more potent anti-neoplastic effects in CRC cell lines deficient in MMR, but mechanisms for such a differential response remain to be established. ©2005 Biochemical Society.


Publication metadata

Author(s): Coxhead JM, Williams EA, Mathers JC

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Conference on Molecular Biology of Colorectal Cancer

Year of Conference: 2005

Pages: 728-729

ISSN: 0300-5127

Publisher: Biochemical Society Transactions, Portland Press Ltd.

URL: http://dx.doi.org/10.1042/BST0330728

DOI: 10.1042/BST0330728

PubMed id: 16042586

Library holdings: Search Newcastle University Library for this item

ISBN: 14708752


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