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

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.