Concentrations of IGF-I and IGFBP-3 and brain tumor risk in the European Prospective Investigation into Cancer and Nutrition.
Rohrmann S., Linseisen J., Becker S., Allen N., Schlehofer B., Overvad K., Olsen A., Tjønneland A., Melin BS., Lund E., Vineis P., Grioni S., Tumino R., Palli D., Mattiello A., Bonet C., Chirlaque MD., Sánchez MJ., Rodríguez L., Dorronsoro M., Ardanaz E., Lagiou P., Trichopoulou A., Trichopoulos D., Dossus L., Grote VA., Boeing H., Aleksandrova K., Bueno-de-Mesquita HB., van Duijnhoven FJ., Peeters PH., Khaw KT., Wareham NJ., Key TJ., Rinaldi S., Romieux I., Gallo V., Michaud DS., Riboli E., Kaaks R.
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.