Article
Genetic polymorphisms of methionine metabolism and susceptibility to brain tumors
Genetische Polymorphismen des Methioninstoffwechsels und Hirntumor-Erkrankungsrisiko
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Published: | May 30, 2008 |
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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.