Article
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
Search Medline for
Authors
Published: | May 8, 2006 |
---|
Outline
Text
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.