gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

A polymorphism of the methionine synthase gene (c.2756A>G, D919G) alters the susceptibility to glioblastoma multiforme

Ein Polymorphismus des Methioninsynthasegens (c.2756A>G, D919G) beeinflusst das Risiko, an einem Glioblastom zu erkranken

Meeting Abstract

  • corresponding author M. Simon - Neurochirurgische Klinik, Universitätsklinikum Bonn
  • A. Semmler - Neurologische Klinik, Universitätsklinikum Bonn
  • S. Moskau - Neurologische Klinik, Universitätsklinikum Bonn
  • M. Linnebank - Neurologische Klinik, Universitätsklinikum Bonn

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 06.77

The electronic version of this article is the complete one and can be found online at:

Published: May 8, 2006

© 2006 Simon et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Glioblastoma multiforme (GBM) is the most common primary brain tumor in humans accounting for up to 15% of all intracranial neoplasms. Genetic factors influencing an individual’s risk to develop a GBM have received relatively little attention by researchers. The c.2756A>G (D919G) polymorphism of the gene coding for 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR, also called methionine synthase) has been correlated with various cancers. In the present study the authors investigated, whether the MTR c.2756A>G polymorphism might also influence the risk to develop a GBM.

Methods: The MTR c.2756A>G polymorphism was genotyped in 213 patients of Caucasian origin with GBM, and in 400 healthy population controls without a history of cancer. Differences between genotype frequencies were tested for statistical significance using the Chi2 test (Pearson’s p, two-sided, α=0.05).

Results: Genotype frequencies closely confirmed to the Hardy-Weinberg equilibrium (p< 0.05) in the patient and in the control group. The MTR c.2756G/G and MTR c.2756A/G genotypes were significantly under-represented in the patient group when compared to the controls (Chi2=13.86; p<0.001), i.e. the MTR c.2756G allele seemed to protect against GBM formation. This association remained highly significant after stratification for age and sex (p<0.001).

Conclusions: This is the first paper reporting a correlation between a genetic polymorphism of the MTR gene and the risk to develop a GBM. The MTR c.2756A>G polymorphism has been shown to influence CpG island methylation as well as global genomic methylation, and may play a role in chromosomal stability, which could explain its role in cancer. Finally, MTR depends for its activity on 5-methyltetrahydrofolate as well as on methylcobalamin. Thus, dietetic factors may modify MTR activity in individuals (and populations), and thereby the incidence of GBMs.