Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma

Lara Bethke, Emily Webb, Anne Murray, Minouk Schoemaker, Maria Feychting, Stefan Lönn, Anders Ahlbom, Beatrice Malmer, Roger Henriksson, Anssi Auvinen, Anne Kiuru, Tiina Salminen, Christoffer Johansen, Helle Collatz Christensen, Kenneth Muir, Patricia McKinney, Sarah Hepworth, Polyxeni Dimitropoulou, Artitaya Lophatananon, Anthony SwerdlowRichard Houlston

47 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Vol/bind17
Udgave nummer5
Sider (fra-til)1195-202
Antal sider8
ISSN1055-9965
DOI
StatusUdgivet - maj 2008
Udgivet eksterntJa

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