title: Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma.
abstract: Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
authors.forename: Lara
authors.initials: L
authors.lastname: Bethke
authors.forename: Emily
authors.initials: E
authors.lastname: Webb
authors.forename: Anne
authors.initials: A
authors.lastname: Murray
authors.forename: Minouk
authors.initials: M
authors.lastname: Schoemaker
authors.forename: Maria
authors.initials: M
authors.lastname: Feychting
authors.forename: Stefan
authors.initials: S
authors.lastname: Lönn
authors.forename: Anders
authors.initials: A
authors.lastname: Ahlbom
authors.forename: Beatrice
authors.initials: B
authors.lastname: Malmer
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
authors.forename: Anne
authors.initials: A
authors.lastname: Kiuru
authors.forename: Tiina
authors.initials: T
authors.lastname: Salminen
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.forename: Helle Collatz
authors.initials: HC
authors.lastname: Christensen
authors.forename: Kenneth
authors.initials: K
authors.lastname: Muir
authors.forename: Patricia
authors.initials: P
authors.lastname: McKinney
authors.forename: Sarah
authors.initials: S
authors.lastname: Hepworth
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Dimitropoulou
authors.forename: Artitaya
authors.initials: A
authors.lastname: Lophatananon
authors.forename: Anthony
authors.initials: A
authors.lastname: Swerdlow
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase