Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma.
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.
Bethke
Lara
L
Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
Webb
Emily
E
Murray
Anne
A
Schoemaker
Minouk
M
Feychting
Maria
M
Lönn
Stefan
S
Ahlbom
Anders
A
Malmer
Beatrice
B
Henriksson
Roger
R
Auvinen
Anssi
A
Kiuru
Anne
A
Salminen
Tiina
T
Johansen
Christoffer
C
Christensen
Helle Collatz
HC
Muir
Kenneth
K
McKinney
Patricia
P
Hepworth
Sarah
S
Dimitropoulou
Polyxeni
P
Lophatananon
Artitaya
A
Swerdlow
Anthony
A
Houlston
Richard
R
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
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