TY - JOUR
T1 - Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma
AU - Bethke, Lara
AU - Webb, Emily
AU - Murray, Anne
AU - Schoemaker, Minouk
AU - Feychting, Maria
AU - Lönn, Stefan
AU - Ahlbom, Anders
AU - Malmer, Beatrice
AU - Henriksson, Roger
AU - Auvinen, Anssi
AU - Kiuru, Anne
AU - Salminen, Tiina
AU - Johansen, Christoffer
AU - Christensen, Helle Collatz
AU - Muir, Kenneth
AU - McKinney, Patricia
AU - Hepworth, Sarah
AU - Dimitropoulou, Polyxeni
AU - Lophatananon, Artitaya
AU - Swerdlow, Anthony
AU - Houlston, Richard
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/genetics
KW - Brain Neoplasms/genetics
KW - Case-Control Studies
KW - Female
KW - Ferredoxin-NADP Reductase/genetics
KW - Folic Acid/metabolism
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Glioma/genetics
KW - Humans
KW - Male
KW - Meningeal Neoplasms/genetics
KW - Meningioma/genetics
KW - Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics
KW - Methylenetetrahydrofolate Reductase (NADPH2)/genetics
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Risk
U2 - 10.1158/1055-9965.EPI-07-2733
DO - 10.1158/1055-9965.EPI-07-2733
M3 - Journal article
C2 - 18483342
SN - 1055-9965
VL - 17
SP - 1195
EP - 1202
JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
IS - 5
ER -