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Lookup NU author(s): Professor John Mathers
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
The purpose of this review article is to examine the evidence of the mechanisms linking obesity with bowel cancer risk and to comment on the development of interventions which that may lower risk of this common age-related disease. The choice of topics for inclusion reflect my personal research on the aetiology and prevention of bowel cancer over the past 3 decades. I have cited literature which addresses each of these topics but, because of the breadth of the review article, I have not attempted to do this systematically. The accumulation of genomic damage which leads to colorectal (bowel) cancer (CRC) is influenced by the balance between damage acquisition through environmental exposures and endogenous factors/ processes and the effectiveness of genomic repair mechanisms. There is now convincing evidence that obesity is associated with increased bowel cancer risk and this increased risk is apparent even among those with Lynch Syndrome who are genetically predisposed to the disease. It seems likely that genomic damage resulting from obesity-related inflammation is a key driver of colorectal tumorigenesis but mechanisms may also include altered insulin/ IGF1 signalling which may give tumour cells a competitive advantage. The importance of inflammation as a mediator of the effects of obesity is supported by the fall in CRC risk which follows sustained exposure to NSAID such as aspirin and the abrogation of the excess CRC risk in obese patients with Lynch Syndrome who were randomised to aspirin. Since the available evidence about the effects of weight loss in the obese on CRC risk is limited, this should be a high priority for future research. In the meantime, to lower the global CRC burden, it would be prudent to institute effective public measures to reduce the development of obesity and to enable those who are obese to lose weight.
Author(s): Mathers JC
Publication type: Article
Publication status: Published
Journal: Nutrition Research
Print publication date: 01/10/2019
Online publication date: 01/09/2018
Acceptance date: 27/08/2018
Date deposited: 03/09/2018
ISSN (print): 0271-5317
ISSN (electronic): 1879-0739
Publisher: Elsevier Inc.
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