Linking Physical Activity to Breast Cancer Risk via Insulin/Insulin-Like Growth Factor Signaling System, Part 1: The Effect of Physical Activity on the Insulin/Insulin-Like Growth Factor Signaling System

Author:

Swain Christopher T.V.1ORCID,Drummond Ann E.1ORCID,Milne Roger L.123ORCID,English Dallas R.12ORCID,Brown Kristy A.4ORCID,Chong Jamie E.5ORCID,Skinner Tina L.5ORCID,van Roekel Eline H.6ORCID,Moore Melissa M.78ORCID,Gaunt Tom R.9ORCID,Martin Richard M.910ORCID,Lewis Sarah J.9ORCID,Lynch Brigid M.1211ORCID

Affiliation:

1. 1Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.

2. 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.

3. 3Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia.

4. 4Department of Medicine, Weill Cornell Medicine, New York, New York.

5. 5The University of Queensland, School of Human Movement and Nutrition Sciences, St. Lucia, Australia.

6. 6Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.

7. 7Medical Oncology, St. Vincent's Hospital, Melbourne, Australia.

8. 8Department of Medicine, The University of Melbourne, Melbourne, Australia.

9. 9Bristol Medical School, University of Bristol, Bristol, United Kingdom.

10. 10IHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom.

11. 11Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.

Abstract

Abstract Physical activity may reduce the risk of developing breast cancer via its effect on the insulin/insulin-like growth factor (IGF) signaling system. A systematic review searched for randomized controlled trials (RCT), Mendelian randomization and prospective cohort studies that examined the effects of physical activity on insulin/IGF signaling [IGFs, their binding proteins (IGFBP), and markers of insulin resistance] in adult women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the Grading of Recommendations Assessment, Development, and Evaluation system used to determine the overall quality of the evidence. Fifty-eight RCTs met our inclusion criteria, no observational or Mendelian randomization studies met the criteria for inclusion. Meta-analyses indicated that physical activity interventions (vs. control) reduced fasting insulin, the Homeostatic Model Assessment for Insulin Resistance and fasting glucose. Physical activity increased IGF-1, but there was no clear effect on IGFBP-3 or the ratio of IGF-1:IGFBP-3. Strong evidence was only established for fasting insulin and insulin resistance. Further research is needed to examine the effect of physical activity on C-peptide and HBA1c in women. Reductions in fasting insulin and insulin resistance following exercise suggest some biological plausibility of the first part of the physical activity–insulin/IGF signaling–breast cancer pathway. See related article by Drummond et al., p. 2116

Funder

Wereld Kanker Onderzoek Fonds

Office of Extramural Research, National Institutes of Health

Cancer Research UK

Victorian Cancer Agency

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

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