Concentrations of IGF-I and IGFBP-3 and brain tumor risk in the European Prospective Investigation into Cancer and Nutrition

Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2174-82. doi: 10.1158/1055-9965.EPI-11-0179. Epub 2011 Jul 25.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / etiology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Case-Control Studies
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Glioma / etiology
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Meningeal Neoplasms / etiology
  • Meningeal Neoplasms / metabolism*
  • Meningeal Neoplasms / pathology
  • Middle Aged
  • Neuroma, Acoustic / etiology
  • Neuroma, Acoustic / metabolism*
  • Neuroma, Acoustic / pathology
  • Nutritional Status
  • Prognosis
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I