Obesity and cancer risk: the role of the insulin-IGF axis
Abstract
Accumulating epidemiological evidence shows that being either overweight or obese, in other words having excess body weight (EBW), is associated with an increased risk of several, common, adult cancers. The molecular mechanisms that underlie these associations are not understood fully, but insulin resistance is likely to be important. The insulin-cancer hypothesis postulates that chronic hyperinsulinemia is associated with decreased concentrations of insulin-like growth factor binding protein1 (IGFBP-1) and IGFBP-2, leading to increased availability of IGF-I and concomitant changes in the cellular environment that favor tumor formation. However, the situation is likely to be more complex because hyperinsulinemia is also associated with alterations in related molecular systems (e.g. sex steroids and adipocytokines). As the prevalence of EBW increases to epidemic proportions, untangling the links between EBW and the insulin-IGF axis and its wider molecular interactions will become increasingly important in the development of preventive strategies.
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Reduced IGFBP-1 and IGFBP-2 increase circulating free bioactive IGF-I.
“Insulin reduces the hepatic production of IGF binding protein (IGFBP)-1 (55,56) and possibly IGFBP-2 (57) with resultant increases in the levels of circulating free, bioactive IGF-I.”
From Diabetes and Cancer (2010) · cites this paper as [57]
Insulin possibly reduces the hepatic production of IGFBP-2.
“Insulin reduces the hepatic production of IGF binding protein (IGFBP)-1 (55,56) and possibly IGFBP-2 (57) with resultant increases in the levels of circulating free, bioactive IGF-I.”
From Diabetes and Cancer (2010) · cites this paper as [57]
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- Authors
- Renehan, A. G., Frystyk, J., & Flyvbjerg, A.
- Affiliations
- The Christie Hospital (GB)
- Aarhus University Hospital (DK)
- Corresponding author
- Renehan, Andrew G.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 17
- Issue
- 8
- Pages
- 328-336
- ISSN
- 1043-2760 (ISSN-L)
- OpenAlex
- W2137989130
- Cited by
- 480
- References
- 71
- Citations by year
- 2026: 2 · 2025: 16 · 2024: 18 · 2023: 21 · 2022: 21 · 2021: 28 · 2020: 26 · 2019: 27 · 2018: 25 · 2017: 27 · 2016: 28 · 2015: 37 · 2014: 32 · 2013: 39 · 2012: 24
- FWCI
- 9.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- obesity, cancer risk, insulin resistance, hyperinsulinemia, insulin-like growth factor I, IGFBP-1, IGFBP-2, sex steroids, adipokines, tumor formation, cancer prevention
- MeSH terms
- Animals, Cross-Sectional Studies, Humans, Insulin, Models, Biological, Models, Theoretical, Neoplasms, Obesity, Risk, Somatomedins, Signal Transduction, Models, Animal
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