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Obesity and bowel cancer: from molecular mechanisms to interventions

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.

Publication metadata

Author(s): Mathers JC

Publication type: Article

Publication status: Published

Journal: Nutrition Research

Year: 2018

Volume: 70

Pages: 26-31

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.


DOI: 10.1016/j.nutres.2018.08.004


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Funder referenceFunder name
Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC) though the Centre for Ageing and Vitality (Grant Reference: MR/L016354/1)