Concentrations of IGF-I and IGFBP-3 and Brain Tumor Risk in the European Prospective Investigation into Cancer and Nutrition

Background: Insulin-like growth factor-1 (IGF-I) is important in normal brain development but in the adult brain, IGF-I overexpression may be a risk factor for tumor development. Methods: We examined the association between circulating concentrations of IGF-I and IGFBP-3 in relation to risk of gliomas (74 low-grade, 206 high-grade gliomas), meningiomas (n = 174) and acoustic neuromas (n = 49) by using a case–control design nested in the European Prospective Investigation into Cancer and Nutrition. IGF-I and IGFBP-3 were measured by ELISAs.Conditional logistic regression was used to compute ORs and corresponding 95% CIs. Results: The risk of low-grade gliomas was elevated with increased IGF-I (OR = 3.60, 95% CI: 1.11–11.7; top vs. bottom quartile) and decreased with elevated IGFBP-3 concentrations (OR = 0.28, 95% CI: 0.09–0.84) after mutual adjustment of these two factors; these results became nonsignificant after exclusion of the first year of follow-up. No association was observed for high-grade gliomas or meningiomas. Both high IGF-I and IGFBP-3 concentrations were associated with risk of acoustic neuromas (IGF-I: OR = 6.63, 95% CI: 2.27–19.4, top vs. bottom tertile; IGFBP-3: OR = 7.07, 95% CI: 2.32–21.6), even after excluding the first year of follow-up. Conclusion: High concentrations of IGF-I might be positively associated with risk of low-grade gliomas and acoustic neuromas, although we cannot exclude reverse causation, in particular for low-grade gliomas. Impact: Factors of the IGF axis might be involved in the etiology of some types of brain tumors. Cancer Epidemiol Biomarkers Prev; 20(10); 2174–82. ©2011 AACR.

[1]  I. Gram,et al.  A cross-sectional analysis of the associations between adult height, BMI and serum concentrations of IGF-I and IGFBP-1 -2 and -3 in the European Prospective Investigation into Cancer and Nutrition (EPIC) , 2011, Annals of human biology.

[2]  Andrew W Roddam,et al.  Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies , 2010, The Lancet. Oncology.

[3]  F. Clavel-Chapelon,et al.  Serum levels of IGF‐I, IGFBP‐3 and colorectal cancer risk: results from the EPIC cohort, plus a meta‐analysis of prospective studies , 2010, International journal of cancer.

[4]  C. Koebnick,et al.  Height, body mass index, and physical activity in relation to glioma risk. , 2009, Cancer research.

[5]  P. Ye,et al.  Expanding the mind: insulin-like growth factor I and brain development. , 2008, Endocrinology.

[6]  François G. Meyer,et al.  Insulin-like Growth Factors, Their Binding Proteins, and Prostate Cancer Risk: Analysis of Individual Patient Data from 12 Prospective Studies , 2008, Annals of Internal Medicine.

[7]  Tarik Tihan,et al.  Brain tumor epidemiology: Consensus from the Brain Tumor Epidemiology Consortium , 2008, Cancer.

[8]  N. Rothman,et al.  Genetic variation in insulin-like growth factors and brain tumor risk. , 2008, Neuro-oncology.

[9]  D. Albanes,et al.  Glioma Risk in Relation to Serum Levels of Insulin-Like Growth Factors , 2007, Cancer Epidemiology Biomarkers & Prevention.

[10]  J. Trojan.,et al.  Insulin-like growth factor type I biology and targeting in malignant gliomas , 2007, Neuroscience.

[11]  Faith G Davis,et al.  Descriptive epidemiology of vestibular schwannomas. , 2006, Neuro-oncology.

[12]  P. Gluckman,et al.  The insulin-like growth factor system and its pleiotropic functions in brain. , 2005, Endocrine reviews.

[13]  A. Gore,et al.  IGF-1 in the Brain as a Regulator of Reproductive Neuroendocrine Function , 2005, Experimental biology and medicine.

[14]  S. Hankinson,et al.  Insulin-like growth factors and neoplasia , 2004, Nature Reviews Cancer.

[15]  Matthias Egger,et al.  Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis , 2004, The Lancet.

[16]  J. Olsen,et al.  Acromegaly and cancer risk: a cohort study in Sweden and Denmark , 2002, Cancer Causes & Control.

[17]  T. Unterman,et al.  Insulin-like growth factors in central nervous system tumors , 1997, Journal of Neuro-Oncology.

[18]  T. Peters,et al.  Do height-related variations in insulin-like growth factors underlie the associations of stature with adult chronic disease? , 2004, The Journal of clinical endocrinology and metabolism.

[19]  P. Eriksson,et al.  Insulin‐like growth factor‐I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro , 2003, Journal of neuroscience research.

[20]  A. Miller,et al.  Overweight, obesity and fat distribution in 50- to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) , 2002, Public Health Nutrition.

[21]  W. Zumkeller IGFs and IGF-binding proteins as diagnostic markers and biological modulators in brain tumors , 2002, Expert review of molecular diagnostics.

[22]  P. Cohen,et al.  Insulin-like growth factor binding protein-3 mediates tumor necrosis factor-alpha-induced apoptosis: role of Bcl-2 phosphorylation. , 2002, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[23]  M. Westphal,et al.  The IGF/IGFBP system in CNS malignancy , 2001, Molecular pathology : MP.

[24]  W. Pan,et al.  Interactions of IGF-1 with the Blood-Brain Barrier in vivo and in situ , 2000, Neuroendocrinology.

[25]  I. McCutcheon,et al.  The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. , 2000, Endocrine reviews.

[26]  P. Cohen,et al.  Insulin-like Growth Factor (IGF)-binding Protein-3 Induces Apoptosis and Mediates the Effects of Transforming Growth Factor-β1 on Programmed Cell Death through a p53- and IGF-independent Mechanism* , 1997, The Journal of Biological Chemistry.

[27]  Elio Riboli,et al.  The EPIC Project: Rationale and study design , 1997 .

[28]  N Slimani,et al.  Pilot phase studies on the accuracy of dietary intake measurements in the EPIC project: overall evaluation of results. European Prospective Investigation into Cancer and Nutrition. , 1997, International journal of epidemiology.

[29]  E Riboli,et al.  The EPIC Project: rationale and study design. European Prospective Investigation into Cancer and Nutrition. , 1997, International journal of epidemiology.

[30]  M. Ocké European prospective investigation into cancer and nutrition. Voedingsnavraag in de EPIC studie. , 1996 .

[31]  D. Clemmons,et al.  Insulin-like growth factors and their binding proteins: biological actions. , 1995, Endocrine reviews.

[32]  F. Naftolin,et al.  Involvement of protein kinase-C in the mitogenic effect of insulin-like growth factor-I on rat astrocytes. , 1992, Endocrinology.