Polymorphisms of methionine metabolism and susceptibility to meningioma formation: laboratory investigation.
OBJECTIVE
Functionally relevant polymorphisms of methionine and folate metabolism have been shown to be associated with various human cancer entities including cerebral lymphoma and glioblastoma multiforme. The authors investigated the association of 7 functional polymorphisms of methionine metabolism with meningioma formation.


METHODS
This case-controlled, monocenter association study included 290 patients of Caucasian origin undergoing surgical resection for intracranial meningioma (World Health Organization [WHO] Grade I, 190 cases; WHO Grade II, 82 cases; WHO Grade III, 18 cases) and 287 age- and sex-matched local controls. The authors analyzed the following genetic variants: dihydrofolate reductase c.594+59del19, 5,10-methylenetetrahydrofolate reductase c.677C > T and c.1298A > C, 5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR) c.2756A > G, reduced folate carrier 1 c.80G > A, cystathionine beta-synthase (CBS) c.844_855ins68 and transcobalamin 2 c.776C > G.


RESULTS
The variant CBS c.844_855ins68 -- that is, the allele carrying the insertion ("ins" or "i") as opposed to the wild-type allele designated as deletion ("del" or "d") -- was significantly overrepresented in meningioma patients (dd/ id/ii: 0.81/0.18/0.01) in comparison with the controls (dd/id/ii: 0.88/0.12/0; 2 df, chi-square 8.97, p = 0.011; multiple nominal regression with age and sex as covariables). In addition, explorative analyses revealed an association of the MTR c.2756A > G variant with meningioma WHO Grade III (AA/AG/GG: patients, 1.0/0/0; controls, 0.64/0.32/0.04; 2 df, chi-square 14.44, p = 0.001).


CONCLUSIONS
The results of this study suggest that genetic variants of methionine metabolism are associated with meningioma formation.
Semmler
Alexander
A
Department of Neurology, University Hospital of Bonn, Germany.
Simon
Matthias
M
Moskau
Susanna
S
Linnebank
Michael
M
D001932:Brain Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008579:Meningioma / Q000235:genetics*; D008715:Methionine / Q000378:metabolism*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D008715:Methionine