Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma
Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma
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DOI：
10.1158/1055-9965.epi-07-2733
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发表时间：
2008-05-01
影响因子：
3.8
通讯作者：
Houlston, Richard
中科院分区：
文献类型：
--
作者：
Bethke, Lara;Webb, Emily;Houlston, Richard
叶酸代谢在肿瘤发生中起重要作用。为了验证叶酸代谢基因5，10-亚甲基四氢叶酸还原酶（MTHFR）、甲硫氨酸合成酶（MTRR）和甲硫氨酸合成酶还原酶（MTR）的多态性变化影响原发性脑肿瘤风险的假设，我们对1,005例胶质瘤病例、631例脑膜瘤病例和1,101例对照进行了MTHFR C677 A和A1298 C、MTRR A66 G、和MTR A2756 G变体。MTHFR C677 T-A1298 C双体型与脑膜瘤（P = 0.002）和胶质瘤（P = 0.02）的风险相关; MTHFR活性降低的基因型风险增加。脑膜瘤的最高风险与两种MTHFR变异的杂合性相关[比值比（OR），2.11; 95%可信区间（95%CI），1.42-3.12]。脑胶质瘤的OR值为1.23（95%CI，0.91-1.66）。还观察到脑膜瘤风险与MTRR 66 G纯合性之间存在显著相关性（OR，1.41; 95%CI，1.02-1.94）。我们的研究结果为叶酸代谢在原发性脑肿瘤发展中的作用提供了支持。特别是，与5，10-亚甲基四氢叶酸水平升高相关的基因型与风险升高相关。
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% Cl, 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.