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叶酸代谢基因的多态性变异与喉癌风险

Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer.

作者信息

Kruszyna Łukasz, Lianeri Margarita, Rydzanicz Małgorzata, Gajecka Marzena, Szyfter Krzysztof, Jagodziński Paweł P

机构信息

Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland.

出版信息

Mol Biol Rep. 2010 Jan;37(1):241-7. doi: 10.1007/s11033-009-9643-y. Epub 2009 Aug 1.

Abstract

Carcinogenesis may result from abnormal methylation of cancer-related genes regulatory sequence. Though, the polymorphic variants of genes encoding enzymes of folate and methionine metabolism may have an effect on DNA methylation. Using PCR-RFLPs, we examined the polymorphism distribution of genes encoding methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1); and methylenetetrahydrofolate reductase (MTHFR) in patients with larynx cancer (n = 131) and controls (n = 250). Patients with MTR 2756AG or GG genotypes displayed a 1.856 -fold increased risk of larynx cancer (95% CI = 1.1860-2.903, P = 0.0076). However, we did not observe an increased risk for the homozygous GG genotype OR = 1.960 (95% CI = 0.6722-5.713, P = 0.2535). Moreover, we did not observe statistical differences in distribution of MTHFR 677C>T, 1298A>C and MTHFD1 1958G>A allele and genotype frequencies in patients and controls. Our findings confirm the significance of the role of the methyl cycle in etiopathogenesis of laryngeal cancer.

摘要

癌症的发生可能源于癌症相关基因调控序列的异常甲基化。然而,编码叶酸和甲硫氨酸代谢酶的基因多态性变体可能会影响DNA甲基化。我们采用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLPs),检测了131例喉癌患者和250例对照者中编码甲硫氨酸合成酶(MTR)、5,10-亚甲基四氢叶酸脱氢酶、5,10-亚甲基四氢叶酸环化水解酶和10-甲酰四氢叶酸合成酶(MTHFD1)以及亚甲基四氢叶酸还原酶(MTHFR)的基因多态性分布。MTR基因2756AG或GG基因型的患者患喉癌的风险增加了1.856倍(95%可信区间=1.1860-2.903,P=0.0076)。然而,我们未观察到纯合GG基因型的风险增加,比值比(OR)=1.96(95%可信区间=0.6722-5.713,P=0.2535)。此外,我们未观察到患者和对照者中MTHFR基因677C>T、1298A>C以及MTHFD1基因1958G>A等位基因和基因型频率分布存在统计学差异。我们的研究结果证实了甲基循环在喉癌病因学中的重要作用。

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