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Rohrmann, S.* ; Linseisen, J. ; Becker, S.* ; Allen, N.* ; Schlehofer, B.* ; Overvad, K.* ; Olsen, A.* ; Tjønneland, A.* ; Melin, B.S.* ; Lund, E.* ; Vineis, P.* ; Grioni, S.* ; Tumino, R.* ; Palli, D.* ; Mattiello, A.* ; Bonet, C.* ; Chirlaque, M.D.* ; Sánchez, M.J.* ; Rodriguez, L.* ; Dorronsoro, M.* ; Ardanaz, E.* ; Lagiou, P.* ; Trichopoulou, A.* ; Trichopoulos, D.* ; Dossus, L.* ; Grote, V.A.* ; Boeing, H.* ; Aleksandrova, K.* ; Bueno-de-Mesquita, H.B.* ; van Duijnhoven, F.J.* ; Peeters, P.H.* ; Khaw, K.T.* ; Wareham, N.J.* ; Key, T.J.* ; Rinaldi, S.* ; Romieux, I.* ; Gallo, V.* ; Michaud, D.S.* ; Riboli, E.* ; Kaaks, R.*

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

Cancer Epidemiol. Biomarkers Prev. 20, 2174-2182 (2011)

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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.

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