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First published on May 22, 2008
This version was published on August 1, 2008
Neuro Oncol 2008 10(4):548-552; DOI:10.1215/15228517-2008-020
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Basic and Translational Investigations

The methylenetetrahydrofolate reductase (MTHFR) variant c.677C>T (A222V) influences overall survival of patients with glioblastoma multiforme

Michael Linnebank, Alexander Semmler, Susanna Moskau, Yvo Smulders, Henk Blom and Matthias Simon

University Hospital Bonn, Department of Neurology, Bonn, Germany (M.L., A.S., S.M.); VU University Hospital Amsterdam, Department of Internal Medicine and Metabolic Unit, Amsterdam, The Netherlands (Y.S., H.B.); University Hospital Bonn, Department of Neurosurgery, Bonn, Germany (M.S.)

Address correspondence to Michael Linnebank, University Hospital Zurich, Department of Neurology, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland (michael.linnebank{at}usz.ch).

Glioblastoma multiforme (GBM) is the most frequent primary brain tumor in adults. Prognosis is poor. Using a series of 214 GBM patients, we observed an effect of the variant 5,10-methylenetetrahydrofolate reductase (MTHFR) c.677C>T on overall survival. This effect was strongest in patients younger than 60 years at diagnosis (overall survival, median ± SE: genotype CC, 13 ± 1 months; CT, 11 ± 2 months; TT, 7 ± 3 months; multivariate Cox regression analysis, Wald = 8.58, p = 0.007). In addition, the MTHFR genotype significantly influenced the overall survival of patients with a postoperative Karnofsky score >70 (CC, 12 ± 2 months; CT, 11 ± 1 months; TT, 10 ± 4 months; Wald = 5.89, p = 0.015). These data suggest the MTHFR c.677C>T variant is a risk factor for survival in GBM patients.

Key Words: glioblastoma • glioma • homocysteine • MTHFR • survival


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Copyright 2008 by Society for Neuro-Oncology