J Korean Neurosurg Soc.  2002 Sep;32(3):183-188.

Genetic Mutation of 5, 10-Methylenetetrahydrofolate Reductase in the Brain Neoplasms

• Ahn JY
• Kim NK
• Han JH
• Kim JK
• Joo JY
• Lee KS

Abstract

OBJECTIVE
Recent epidermiologic studies suggested that alterations in folate metabolism as a result of polymorphism in the enzyme 5,10-methylenetetrahydrofolate reductase(MTHFR) have been frequently associated with neural tube defects, vascular disease, and some cancers. A common 677C->T polymorphism in the MTHFR gene results in thermolability and reduced MTHFR activity that decreases the pool of 5-methyltetrahydrofolate and increases the pool of 5,10-methylenetetrahydrofolate. A possible cause underlying altered DNA methylation could be an insufficient level of S-adenosylmethionine as a consequence of weaker alleles of MTHFR gene. Therefore, the weak MTHFR activity may underlie susceptibility to brain neoplasms. We now report the associations of MTHFR polymorphisms in three groups of adult brain tumors: gliomas, meningiomas and schwannomas.
METHODS
We analyzed DNA of 71 brain tumors and 254 age- and sex-matched controls with a case-control study. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay.
RESULTS
The incidence of the MTHFR 677TT genotype was higher among 20 schwannoma cases compared with that of 254 controls, conferring a 5-fold increase of the risk of schwannomas(odds ratio, OR=4.75 ; 95% confidence index, CI=1.05-21.50). The homozygous mutant group had half the risk of meningioma(OR=0.42:95% CI = 0.11-1.58) compared with the homozygous normal or heterozygous genotypes. There was no significant difference in MTHFR 677TT genotype frequency between glioma group(19 cases) and control group(254 cases)(OR = 1.53 ; 95% CI = 0.30-7.73).
CONCLUSION
The data indicate that the homozygous 677TT MTHFR genotype confers the significantly higher risk of schwannoma and the lower risk of meningioma. However, our study had limited a statistical power because of the small sample size, which is reflected in the wide CIs. Hence, these findings need to be confirmed in larger populations.

Keyword

Brain neoplasms; Folic acid; Methylenetetrahydrofolate reductase; Polymorphism; Risk factors

MeSH Terms

Adult
Alleles
Brain Neoplasms*
Brain*
Case-Control Studies
DNA
DNA Methylation
Folic Acid
Genotype
Glioma
Humans
Incidence
Meningioma
Metabolism
Methylenetetrahydrofolate Reductase (NADPH2)
Neural Tube Defects
Neurilemmoma
Oxidoreductases*
Risk Factors
S-Adenosylmethionine
Sample Size
Vascular Diseases
DNA
Folic Acid
Methylenetetrahydrofolate Reductase (NADPH2)
Oxidoreductases
S-Adenosylmethionine