Could Reducing Body Fatness Reduce the Risk of Aggressive Prostate Cancer via the Insulin Signalling Pathway? A Systematic Review of the Mechanistic Pathway.

Rachel James,Olympia Dimopoulou,Stefan Brugger,Julian P T Higgins,Richard M Martin,Claire M Perks,Sarah J Lewis,Louise Mathias,Claire Kelly

doi:10.3390/metabo11110726

Rachel James, Olympia Dimopoulou + Show 7 more

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https://doi.org/10.3390/metabo11110726

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Journal: Metabolites	Publication Date: Oct 23, 2021
Citations: 1	License type: CC BY 4.0

Affiliation: University of Bristol, Medical Research Council

Abstract

Excess body weight is thought to increase the risk of aggressive prostate cancer (PCa), although the biological mechanism is currently unclear. Body fatness is positively associated with a diminished cellular response to insulin and biomarkers of insulin signalling have been positively associated with PCa risk. We carried out a two-pronged systematic review of (a) the effect of reducing body fatness on insulin biomarker levels and (b) the effect of insulin biomarkers on PCa risk, to determine whether a reduction in body fatness could reduce PCa risk via effects on the insulin signalling pathway. We identified seven eligible randomised controlled trials of interventions designed to reduce body fatness which measured insulin biomarkers as an outcome, and six eligible prospective observational studies of insulin biomarkers and PCa risk. We found some evidence that a reduction in body fatness improved insulin sensitivity although our confidence in this evidence was low based on GRADE (Grading of Recommendations, Assessment, Development and Evaluations). We were unable to reach any conclusions on the effect of insulin sensitivity on PCa risk from the few studies included in our systematic review. A reduction in body fatness may reduce PCa risk via insulin signalling, but more high-quality evidence is needed before any conclusions can be reached regarding PCa.

Highlights

Prostate cancer (PCa) is the leading cause of morbidity and mortality in men worldwide [1]
Our objective was to systematically review and synthesise evidence from studies investigating whether changing body fatness might impact on PCa risk via the insulin signalling pathway; in doing so, we investigated the insulin signalling pathway as a potential mechanistic link between body fatness and PCa incidence or progression
After removing duplicates and screening studies for eligibility, we identified seven eligible studies [32,33,34,35,36,37,38] where a reduction in body fatness was the exposure and at least one biomarker of insulin sensitivity was reported as an outcome (Figure 1)

Summary

Introduction

Prostate cancer (PCa) is the leading cause of morbidity and mortality in men worldwide [1]. In 2018, there were 1.28 million newly diagnosed PCas, making the disease the second most commonly occurring cancer in men [2]. Excess body weight, resulting from imbalances in diet and physical activity, has been implicated as a risk factor for the incidence and progression of several cancers including. In 2012, overweight and obesity, characterised by excess body fat, w estimated to contribute to 3.9% of all incident cancers, a figure expected to rise in the few decades given current trends in this risk factor [6]. Whilst the association with localised PCa remains inconsistent, evidence has shown that body fatness is positively associated with aggressive

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