School of Public Health, Taipei Medical University, Taipei, Taiwan.
Cancer Causes Control. 2010 Oct;21(10):1605-13. doi: 10.1007/s10552-010-9589-3. Epub 2010 Jun 8.
Gene polymorphisms in the one-carbon metabolism pathway could contribute to arsenic methylation capability through plasma folate and homocysteine metabolism, thereby increasing the susceptibility to urothelial carcinoma (UC) risk.
The goal of our study was to evaluate the roles of gene polymorphisms in the one-carbon metabolism pathway in the carcinogenesis of UC.
A hospital-based case-controlled study was conducted. The urinary arsenic profile was examined using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Folate levels were measured using a competitive immunoassay kit. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism technique.
Patients with UC had higher urinary total arsenic, inorganic arsenic percentage (InAs%) and monomethylarsenic acid percentage (MMA%), and lower dimethylarsenic acid percentage (DMA%), plasma folate and homocysteine levels than controls. The correlations between folate and DMA%, and folate and homocysteine, were significant according to Pearson's correlation coefficients. Subjects carrying the 5,10-methylenetetrahydrofolate reductase (MTHFR) CT or TT genotype had a lower DMA% and lower folate levels than those carrying the CC genotype. Participants with the methionine synthase (MS) AA genotype had higher homocysteine levels than those with the AG or GG genotype. However, neither MTHFR nor MS gene polymorphisms were associated with UC risk.
Environmental factors played a more important role in UC carcinogenesis than MTHFR or MS gene polymorphism.
一碳代谢途径中的基因多态性可能通过血浆叶酸和同型半胱氨酸代谢影响砷的甲基化能力，从而增加患膀胱癌（UC）的风险。
本研究旨在评估一碳代谢途径中基因多态性在 UC 发生发展中的作用。
采用基于医院的病例对照研究。采用高效液相色谱和氢化物发生器-原子吸收光谱法检测尿砷形态。采用竞争免疫试剂盒检测叶酸水平。采用聚合酶链反应-限制性片段长度多态性技术进行基因分型。
与对照组相比，UC 患者的尿总砷、无机砷百分比（InAs%）和一甲基砷酸百分比（MMA%）较高，二甲基砷酸百分比（DMA%）、血浆叶酸和同型半胱氨酸水平较低。根据 Pearson 相关系数，叶酸与 DMA%和叶酸与同型半胱氨酸之间存在显著相关性。与 CC 基因型相比，携带 5,10-亚甲基四氢叶酸还原酶（MTHFR）CT 或 TT 基因型的受试者 DMA%和叶酸水平较低。携带蛋氨酸合成酶（MS）AA 基因型的参与者同型半胱氨酸水平高于携带 AG 或 GG 基因型的参与者。然而，MTHFR 或 MS 基因多态性均与 UC 风险无关。
与 MTHFR 或 MS 基因多态性相比，环境因素在 UC 致癌作用中发挥了更为重要的作用。
