C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in meningiomas and high-grade gliomas.

Abstract

Background: Methylenetetrahydrofolate reductase (MTHFR) plays a role in DNA biosynthesis, methylation and repair in actively dividing cells by acting on folate metabolism. A common C677T polymorphism in the gene for MTHFR leads to an enzyme with decreased activity. MTHFR polymorphisms have been studied in various cancers but not in primary brain tumors. The purpose of this case-control study was to explore a possible association between MTHFR C677T polymorphism and primary brain tumors. Materials and Methods: The MTHFR C677T genotype was determined in 74 patients with histologically-verifred primary brain tumors and 98 cancer free control subjects. Results: The MTHFR 677T variant genotype was observed in 49% of cases and 46% of controls. Although the difference was not significant (p=0.194), the homozygous TT genotype was found at a higher frequency in high-grade glioma (HGG) patients compared to controls (15.4% and 7.1%, respectively). The MTHFR genotype was not associated with meningioma patients. Defining patients with the CC genotype as reference, the relative risk of HGG for subjects with the T allele (CT+TT genotype) was 1.17. Conclusion: In spite of the established effect of the MTHFR 677 TT genotype on DNA hypomethylation with concomitant inadequate folate levels, the MTHFR 677 TT genotype is not associated with individual susceptibility to HGG.