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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA081188-03 Interpret this number
Primary Investigator: Kaaks, Rudolf
Organization: International Agency For Res On Cancer
Project Title: Insulin, Igf-1 & Cancers of Breast, Endometrium & Ovary
Fiscal Year: 2001
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Abstract

A Western lifestyle, including type of diet, lack of physical activity, and certain childbearing patterns, is associated with high risks of cancers of the breast, endometrium, and ovary. A widely held view is that effects of lifestyle factors on cancer risk are mediated through alterations in hormone metabolism. One feature potentially shared by all three forms of cancer is ovarian overproduction of androgens. A second common feature may be elevated plasma and tissue levels of insulin or insulin-like growth factor-I (IGF-I), or decreased IGF-binding proteins. Insulin is a key hormone in the regulation of energy metabolism and, together with insulin-like growth factor-I, is also central in the regulation of anabolic (growth) processes as function of available energy and elementary substrates (e.g., amino acids). Increased levels of IGF-I, or decreased levels of IGF-binding proteins (IGFBPs), have been shown to promote tumor development by inhibiting apoptosis, and by stimulating cell proliferatton. In addition, insulin and IGF-I enhance ovarian androgen production and down regulate hepatic production and plasma levels of SHBG. The specific aim of the present proposal is to address the hypothesis that increased (prediagnostic) plasma levels of insulin; and/or increased plasma IGF-I for given concentrations of major IGFBPs (IGFBP-1, -2, -3) are associated with increased risk of ovarian and endometrial cancers and of breast cancer in young women. Through insulin and IGF-I, the study seeks to establish a linkage between exposure to Western lifestyle and over nutrition and imbalances in steroid hormones that are thought to be associated with the three cancers most frequently affecting women. This study is a component (Component 3) of a group of three concurrent studies which address complementary aspects of the role of endogenous hormones in the etiology of ovarian and endometrial cancers, and of breast cancer in young women. All studies are based on the same underlying population, obtained by combining three prospective cohort studies that are currently ongoing in New York, Umea (Sweden) and Milan (Italy).

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Publications

Igf-i, Igfbp-3 And Breast Cancer In Young Women: A Pooled Re-analysis Of Three Prospective Studies
Authors: Rinaldi S. , Toniolo P. , Muti P. , Lundin E. , Zeleniuch-Jacquotte A. , Arslan A. , Micheli A. , Lenner P. , Dossus L. , Krogh V. , et al. .
Source: European Journal Of Cancer Prevention : The Official Journal Of The European Cancer Prevention Organisation (ecp), 2005 Dec; 14(6), p. 493-6.
PMID: 16284492
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Insulin-like Growth Factor-i, Igf Binding Protein-3, And Breast Cancer In Young Women: A Comparison Of Risk Estimates Using Different Peptide Assays
Authors: Rinaldi S. , Kaaks R. , Zeleniuch-Jacquotte A. , Arslan A.A. , Shore R.E. , Koenig K.L. , Dossus L. , Riboli E. , Stattin P. , Lukanova A. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2005 Jan; 14(1), p. 48-52.
PMID: 15668475
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Endogenous Hormones And Ovarian Cancer: Epidemiology And Current Hypotheses
Authors: Lukanova A. , Kaaks R. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2005 Jan; 14(1), p. 98-107.
PMID: 15668482
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Body Mass Index, Circulating Levels Of Sex-steroid Hormones, Igf-i And Igf-binding Protein-3: A Cross-sectional Study In Healthy Women
Authors: Lukanova A. , Lundin E. , Zeleniuch-Jacquotte A. , Muti P. , Mure A. , Rinaldi S. , Dossus L. , Micheli A. , Arslan A. , Lenner P. , et al. .
Source: European Journal Of Endocrinology / European Federation Of Endocrine Societies, 2004 Feb; 150(2), p. 161-71.
PMID: 14763914
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Prediagnostic Levels Of C-peptide, Igf-i, Igfbp -1, -2 And -3 And Risk Of Endometrial Cancer
Authors: Lukanova A. , Zeleniuch-Jacquotte A. , Lundin E. , Micheli A. , Arslan A.A. , Rinaldi S. , Muti P. , Lenner P. , Koenig K.L. , Biessy C. , et al. .
Source: International Journal Of Cancer, 2004-01-10 00:00:00.0; 108(2), p. 262-8.
PMID: 14639613
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Serum Follicle-stimulating Hormone And Risk Of Epithelial Ovarian Cancer In Postmenopausal Women
Authors: Arslan A.A. , Zeleniuch-Jacquotte A. , Lundin E. , Micheli A. , Lukanova A. , Afanasyeva Y. , Lenner P. , Krogh V. , Muti P. , Rinaldi S. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2003 Dec; 12(12), p. 1531-5.
PMID: 14693749
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Reliability Of Follicle-stimulating Hormone Measurements In Serum
Authors: Arslan A.A. , Zeleniuch-Jacquotte A. , Lukanova A. , Rinaldi S. , Kaaks R. , Toniolo P. .
Source: Reproductive Biology And Endocrinology : Rb&e, 2003-06-18 00:00:00.0; 1, p. 49.
PMID: 12844363
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Circulating Levels Of Sex Steroid Hormones And Risk Of Ovarian Cancer
Authors: Lukanova A. , Lundin E. , Akhmedkhanov A. , Micheli A. , Rinaldi S. , Zeleniuch-Jacquotte A. , Lenner P. , Muti P. , Biessy C. , Krogh V. , et al. .
Source: International Journal Of Cancer, 2003-05-01 00:00:00.0; 104(5), p. 636-42.
PMID: 12594820
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Risk Of Ovarian Cancer In Relation To Prediagnostic Levels Of C-peptide, Insulin-like Growth Factor Binding Proteins-1 And -2 (usa, Sweden, Italy)
Authors: Lukanova A. , Lundin E. , Micheli A. , Akhmedkhanov A. , Rinaldi S. , Muti P. , Lenner P. , Biessy C. , Krogh V. , Riboli E. , et al. .
Source: Cancer Causes & Control : Ccc, 2003 Apr; 14(3), p. 285-92.
PMID: 12814208
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Obesity, Endogenous Hormones, And Endometrial Cancer Risk: A Synthetic Review
Authors: Kaaks R. , Lukanova A. , Kurzer M.S. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2002 Dec; 11(12), p. 1531-43.
PMID: 12496040
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Circulating Levels Of Insulin-like Growth Factor-i And Risk Of Ovarian Cancer
Authors: Lukanova A. , Lundin E. , Toniolo P. , Micheli A. , Akhmedkhanov A. , Rinaldi S. , Muti P. , Lenner P. , Biessy C. , Krogh V. , et al. .
Source: International Journal Of Cancer, 2002-10-20 00:00:00.0; 101(6), p. 549-54.
PMID: 12237896
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