gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

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Genetic polymorphisms of methionine metabolism and susceptibility to brain tumors

Genetische Polymorphismen des Methioninstoffwechsels und Hirntumor-Erkrankungsrisiko

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

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocDI.03.09

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2008/08dgnc166.shtml

Published: May 30, 2008

© 2008 Simon et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Genetic instability, genomic hypomethylation and epigenetic silencing through promoter DNA hypermethylation are hallmarks of cancer development and progression. The methionine metabolism plays a central role in DNA synthesis and repair, and DNA methylation. Several functional polymorphisms of methionine metabolism have been associated with an increased incidence of various human cancers. The authors have investigated whether such associations may also exist for brain tumors.

Methods: We investigated 328 consecutive glioblastoma multiforme (GBM) patients, 290 meningioma patients, and 31 primary central nervous system lymphoma (PCNSL) patients of Caucasian origin. Different populations of age- and gender-matched Caucasian area residents without a history of cancer served as controls. Genotyping of the 5,10-methylenetetrahydrofolate reductase (MTHFR) c.677C>T and c.1298A>C, 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR) c.2756A>G, reduced folate carrier 1 (RFC1) c.80G>A, cystathionine beta-synthase (CBS) c.833T>C and 844ins68, transcobalamin 2 (Tc2) c.776C>G and dihydrofolate reductase (DHFR) c.594+59del19 polymorphisms was performed using PCR and appropriate restriction digests.

Results: In GBM, PCNSL and meningioma WHO grade III patients the G-allele of MTR c.2756A>G was significantly under-represented (GBM: p<0.001; PCNSL: p<0.005; meningioma WHO III: p=0.001), suggesting a protective effect of the G-allele in malignant brain tumors. In addition, we found an association between meningiomas (all WHO grades) and the CBS844ins68 polymorphism (p=0.01).

Conclusions: Our data suggest a role for functional genetic variants of methionine metabolism and therefore variations of methionine metabolism in a more general sense in the pathogenesis of brain tumors. Nutritional intake is a key determinant of methionine metabolism. Hence, nutritional measures may influence the risk to develop certain brain tumors.