Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies
Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies
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DOI：
10.1016/j.leukres.2008.07.026
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Kim, Hyeoung-Joon
中科院分区：
文献类型：
--
作者：
Kim, Hee Nam;Kim, Yeo-Kyeoung;Kim, Hyeoung-Joon
编码叶酸代谢酶的基因中的一些遗传多态性与血液恶性肿瘤的易感性有关。我们进行了一项基于韩国人群的病例对照研究，以检查叶酸代谢酶多态性与AML（急性髓性白血病）、CML（慢性髓性白血病）、MDS（骨髓痉挛障碍综合征）和ALL（急性淋巴细胞白血病）风险之间的关系。MTHFR 677TT基因型与ALL风险增加相关(优势比(OR) = 1.77；95%置信区间(CI) = 1.02-3.09, p = 0.044)。MTRR 66 AG基因型与MDS风险增加相关（OR = 1.59; 1.06-2.38, p = 0.026）， MTRR 66 GG基因型与AML风险增加相关（OR = 1.51; 1.03-2.23, p = 0.037）。TYMS 2R3R基因型与AML风险降低相关（OR = 0.76; 0.60-0.96, p = 0.022）。TYMS hap3 （2R-6bp）和hap4 （2R-Obp）分别与AML风险降低（OR = 0.69; 0.53-0.90, p = 0.006）和风险增加（OR = 1.65; 1.20-2.27, p = 0.002）相关。Hap C （677T-1298A）与ALL风险增加相关（OR = 1.40; 1.02-1.92, p = 0.04）。ALL的风险似乎与MTHFR 677多态性有关。结果支持韩国几种血液恶性肿瘤中叶酸多态性的风险改变。结果模式表明MDS与DNA甲基化状态相关，AML的风险与DNA合成和DNA甲基化状态相关。(C) 2008 Elsevier Ltd版权所有。
Several genetic polymorphisms in the genes coding folate-metabolizing enzymes have been associated with susceptibility to hematology malignancies. We conducted a Korean population-based case-control study to examine the relationship between the polymorphisms of folate-metabolizing enzymes and the risk of AML (acute myelogenous leukemia), CML (chronic myelogenous leukemia), MDS (myelodyspastic syndrome), and ALL (acute lymphoblastc leukemia).The MTHFR 677TT genotype was associated with an increased risk for ALL (odds ratios (OR) = 1.77; 95% confidence intervals (CI) = 1.02-3.09, p = .044). The MTRR 66 AG genotype was associated with an increased risk for MDS (OR = 1.59; 1.06-2.38, p = .026) and the MTRR 66 GG genotype was associated with increased risk for AML (OR = 1.51; 1.03-2.23, p = .037). The TYMS 2R3R genotype was associated with a decreased risk for AML (OR = 0.76; 0.60-0.96, p = .022). The TYMS hap3 (2R-6bp) and hap4 (2R-Obp) were associated with decreased risk (OR = 0.69; 0.53-0.90, p = .006) and increased risk (OR = 1.65; 1.20-2.27, p = .002), respectively for AML. Hap C (677T-1298A) was associated with an increased risk (OR = 1.40; 1.02-1.92, p = .04) for ALL. The risk for ALL appears to be associated with the MTHFR 677 polymorphism. The results are supportive of a risk modification by folate polymorphisms in several hematologic malignancies in Korea. The pattern of results suggests that MDS was associated with the DNA methylation status and the risk for AML was associated with both the DNA synthesis and DNA methylation status. (C) 2008 Elsevier Ltd. All rights reserved.