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. 2008 Aug;10(4):548-52.
doi: 10.1215/15228517-2008-020. Epub 2008 May 22.

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

Michael Linnebank  1 , Alexander Semmler, Susanna Moskau, Yvo Smulders, Henk Blom, Matthias Simon
Affiliations

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

Michael Linnebank et al. Neuro Oncol. 2008 Aug.

Abstract

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.

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Figures

Fig. 1
Fig. 1
Human methionine metabolism. Methionine becomes activated to S-adenosylmethionine (SAM) via methionine adenosyltransferase (MAT). SAM is a ubiquitous methyl group donor, for example, for the synthesis of biogenic amines and DNA methylation. The degradation product of SAM is S-adenosylhomocysteine (SAH), which is hydrolyzed to homocysteine via homocysteine hydrolase (SAHH). Homocysteine can be transsulfurated to cystathionine and cysteine via vitamin B6–dependent cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CGL); alternatively, homocysteine can be remethylated to methionine via 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR; also called methionine synthase), which needs a derivate of vitamin B12 (methylcobalamin) and a derivate of folate (5-methyltetrahydrofolate; 5-CH3-FH4) as cofactors. Vitamin B12 is transported by transcobalamin 2 (Tc2), and 5-CH3-FH4 is synthesized by flavin adenine dinucleotide (FAD)–dependent 5,10-methylenetetrahydrofolate reductase (MTHFR) from 5,10-methylenetetrahydrofolate (5,10-CH2-FH4), which is synthesized from folate by dihydrofolate reductase (DHFR) in two subsequent steps.
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