Methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms and reduced risk of malignant lymphoma
Methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms and reduced risk of malignant lymphoma
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DOI：
10.1002/ajh.20215
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发表时间：
2004-12-01
影响因子：
12.8
通讯作者：
Tajima, K
中科院分区：
文献类型：
--
作者：
Matsuo, K;Hamajima, N;Tajima, K
叶酸和蛋氨酸是“一碳”代谢中的重要营养物质，与DNA合成和DNA甲基化密切相关。这些途径的遗传变异可能会改变癌症发展的易感性。我们之前报道过淋巴瘤风险与亚甲基四氢叶酸还原酶（MTHFR C677T 和 A1298C）和甲硫氨酸合酶（MTR A2756G）基因种系多态性之间的关联，发现除 MTHFR 677CC/1298AA 之外的基因型与 MTHFR 相比，其风险为一半 677CC/1298AA，MTR GG 基因型的风险比 AA/AG 基因型高 3 倍。为了证实这种关联并探索组织学差异，我们扩展了之前的病例系列。日本进行了一项病例对照研究，共检查了 372 例淋巴瘤病例和 500 例非癌症对照的基因型。通过无条件逻辑回归分析估计相对风险。在总体分析中，携带 MTHFR 677T 或 1298C 等位基因的受试者相对于 677CC/1298AA 基因型的年龄-性别调整优势比 (OR) 为 0.58（95% 置信区间：0.41-0.83，P = 0.002）。 MTR GG 基因型的 OR 为 1.75 (0.87-3.52, P = 0.114)。这些发现在对 273 个新事件案例的单独分析中得到了验证。根据组织学亚型[弥漫性大 B 细胞淋巴瘤 (DLB)、滤泡性淋巴瘤 (FL)、粘膜相关淋巴组织低度淋巴瘤 (MALT) 等] 进行的亚组分析表明，除了 FL 和 MALT 的某些例外之外，存在类似的关联。我们的数据显示，MTHFR 多态性与所有组织学亚型的恶性淋巴瘤风险之间存在关联，尽管这些多态性的贡献程度可能因组织学亚型而有所不同。还证实了与 MTR 多态性缺乏关联。 (C) 2004 Wiley-Liss, Inc.
Folate and methionine are important nutrients in the "one-carbon" metabolism that is closely associated with DNA synthesis and DNA methylation. Genetic variation in these pathways may change susceptibility to cancer development. We have previously reported associations between lymphoma risk and germline polymorphisms in genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase (MTR A2756G), finding the genotype other than the MTHFR 677CC/1298AA to confer a half-risk compared, to the MTHFR 677CC/1298AA and a 3-fold higher risk with the MTR GG genotype than the AA/AG genotypes. To confirm the association and explore the histological difference, we extended the previous case series. A case-control study was conducted in Japan with a total of 372 lymphoma cases and 500 noncancer controls examined for genotypes. The relative risks were estimated by unconditional logistic regression analysis. In overall analyses, the age-sex adjusted odds ratio (OR) for the subjects harboring MTHFR 677T or 1298C alleles relative to 677CC/1298AA genotype was 0.58 (95% confidence interval: 0.41-0.83, P = 0.002). The MTR GG genotype showed an OR of 1.75 (0.87-3.52, P = 0.114). These findings were validated in separate analyses of the 273 new incident cases. Subgroup analyses according to histological subtype [diffuse large B-cell lymphoma (DLB), follicular lymphoma (FL), low-grade lymphoma of mucosa associated lymphoid tissue (MALT), and others] illustrated similar associations with certain exceptions for FL and MALT. Our data showed an association between the MTHFR polymorphisms and malignant lymphoma risk for all histological subtypes, although the extent of contribution of these polymorphisms may differ somewhat with histological subtype. Lack of association with MTR polymorphism was also confirmed. (C) 2004 Wiley-Liss, Inc.