Grant Number:	5R01CA102460-03 Interpret this number
Primary Investigator:	Kaaks, Rudolf
Organization:	International Agency For Res On Cancer
Project Title:	Lifestyle, Insulin, Igf-I and Colorectal Cancer
Fiscal Year:	2005

DESCRIPTION (provided by applicant): A Western lifestyle, characterized by a low level of physical activity, and an energy-dense diet rich in easily digestible (refined) carbohydrates and fats, is associated with an increased risk of developing colon cancer. Etiologic models to explain this association have focused mostly on effects of diet on exposures of the colonic rnucosa to mutagenic or tumor-promoting compounds in the gut lumen. A limitation of these models is that they do not explain the inverse relation of risk with physical activity or the positive relation of risk with obesity. A more recent theory states that effects of a Western lifestyle on colon cancer risk may at least in part be mediated by alterations in the metabolism of insulin and insulin-like growth factors (IGFs). Insulin is a key hormone in the regulation of energy metabolism. It increases the bio-activity of IGF-I by enhancing its synthesis, and by down regulating several of its binding proteins (IGFBP-1 and -2). Insulin and IGF-I both stimulate anabolic (growth) processes, as a function of available energy and elementary substrates (e.g., amino acids). In excess, the anabolic signals by insulin or IGF-I can promote tumor development by inhibiting apoptosis, and by stimulating cell proliferation. Overeating and obesity tend to increase plasma insulin and bio-active IGF-I, whereas plasma insulin and total and bioavailable IGF-I are decreased by energy restriction, which protects against many forms of cancer in animal models. The specific aims of the present study are: [1] to examine whether increased (prediagnostic) serum levels of glycated hemoglobin (a marker for plasma glucose) and C-peptide (a marker for insulin levels), and low levels of IGFBP-1 and IGFBP-2, increase risk of colon cancer, and possibly rectal cancer; [2] to examine whether elevated IGF-I concentrations (absolute, or relative to its major plasmatic binding protein -- IGFBP-3) are increase risk of colon and rectal cancers; [3] to examine whether high dietary glycemic load increases colorectal cancer risk ; and [4] to describe relationships of diet (particularly glycemic load), anthropometric indices, and other lifestyle variables with each of the serum peptides. This study seeks to increase understanding of etiologic mechanisms relating over nutrition to colon cancer development, which will eventually allow the in formulation of more precise nutritional guidelines for efficient prevention.




A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).
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Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study.
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Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies.
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Methodological challenges in the application of the glycemic index in epidemiological studies using data from the European Prospective Investigation into Cancer and Nutrition.
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Glycosylated hemoglobin and risk of colorectal cancer in men and women, the European prospective investigation into cancer and nutrition.
Authors: Rinaldi S. , Rohrmann S. , Jenab M. , Biessy C. , Sieri S. , Palli D. , Tumino R. , Mattiello A. , Vineis P. , Nieters A. , et al. .
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Authors: Jenab M. , Riboli E. , Cleveland R.J. , Norat T. , Rinaldi S. , Nieters A. , Biessy C. , Tjønneland A. , Olsen A. , Overvad K. , et al. .
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