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Energy balance and cancer: the role of insulin and insulin-like growth factor-I

Published online by Cambridge University Press:  28 February 2007

R. Kaaks  and
A. Lukanova
R. Kaaks*
Affiliation:
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France
A. Lukanova
Affiliation:
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France
*
*Corresponding author: Dr R. Kaaks, fax +33 4 72 73 83 61, email kaaks@iarc.fr
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Abstract

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Recent theories propose that a Western lifestyle may increase cancer risk through alterations in the metabolism of insulin and insulin-like growth factors (IGF; McKeown-Eyssen, 1994; Giovannucci, 1995; Kaaks, 1996; Werner & LeRoith, 1996). Insulin regulates energy metabolism, and increases the bioactivity of IGF-I, by enhancing its synthesis, and by decreasing several of its binding proteins (IGFBP; IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic processes as a function of available energy and elementary substrates (e.g. amino acids). The anabolic signals by insulin or IGF-I can promote tumour development by inhibiting apoptosis, and by stimulating cell proliferation. Furthermore, both insulin and IGF-I stimulate the synthesis of sex steroids, and inhibit the synthesis of sex hormone-binding globulin (SHBG), a binding protein that regulates the bioavailability of circulating sex steroids to tissues. The present paper reviews epidemiological findings relating the risk of cancers of the colo-rectum, pancreas, breast, endometrium and prostate to body size (obesity, height) and physical activity, and discusses the relationships between obesity and physical activity and plasma levels of insulin, IGF-I and IGFBP. Subsequent sections review epidemiological findings relating cancer risk to indices of chronic hyperinsulinaemia, and to plasma levels of IGF-I and IGFBP. Conclusions are that chronic hyperinsulinaemia may be a cause of cancers of the colon, pancreas and endometrium, and also possibly of the breast. On the other hand, elevated plasma IGF-I, as total concentrations or relative to levels of IGFBP-3, appears to be related to an increased risk of prostate cancer, breast cancer in young women, and possibly colo-rectal cancer. For cancers of the endometrium, breast and prostate, these findings are discussed in the context of relationships between insulin and IGF-I and levels of bioavailable sex steroids.

Keywords

CancerInsulinInsulin-like growth factorsEnergy balance
Type
Macronutrient Metabolism Group Symposium on ‘Energy flux and cancer’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 1 , February 2001 , pp. 91 - 106
Copyright
Copyright © The Nutrition Society 2001

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