Obesity and cancer: existing and new hypotheses for a causal connection

Stone, T. W. , McPherson, M. and Darlington, L. G. (2018) Obesity and cancer: existing and new hypotheses for a causal connection. EBioMedicine, 30, pp. 14-28. (doi: 10.1016/j.ebiom.2018.02.022) (PMID:29526577) (PMCID:PMC5952217)

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Existing explanations of obesity-associated cancer emphasise direct mutagenic effects of dietary components or hormonal imbalance. Some of these hypotheses are reviewed briefly, but recent evidence suggests a major role for chronic inflammation in cancer risk, possibly involving dietary content. These ideas include the inflammation-induced activation of the kynurenine pathway and its role in feeding and metabolism by activation of the aryl hydrocarbon receptor (AHR) and by modulating synaptic transmission in the brain. Evidence for a role of the kynurenine pathway in carcinogenesis then provides a potentially major link between obesity and cancer. A second new hypothesis is based on evidence that serine proteases can deplete cells of the tumour suppressors Deleted in Colorectal Cancer (DCC) and neogenin. These enzymes include mammalian chymotryptic proteases released by pro-inflammatory neutrophils and macrophages. Blood levels of chymotrypsin itself increase in parallel with food intake. The mechanistically similar bacterial enzyme subtilisin is widespread in the environment, animal probiotics, meat processing and cleaning products. Simple public health schemes in these areas, with selective serine protease inhibitors and AHR antagonists and could prevent a range of intestinal and other cancers.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Stone, Professor Trevor and Darlington, Dr Lynda
Authors: Stone, T. W., McPherson, M., and Darlington, L. G.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:EBioMedicine
ISSN (Online):2352-3964
Published Online:27 February 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in EBioMedicine 30: 14-28
Publisher Policy:Reproduced under a Creative Commons License

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