Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Arch Toxicol. 2019 Aug;93(8):2155-2164. doi: 10.1007/s00204-019-02500-y. Epub 2019 Jul 30.
Environmental exposure to arsenic may be involved in the disturbance of DNA hypomethylation. The aim of this study is the first to explore the effect of interactions of urinary total arsenic levels, arsenic methylation capacity, 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma folate, and global 5-methyl-2'-deoxycytidine (5-MedC) levels on the risk of urothelial carcinoma (UC). A hospital-based case-control study was constructed. The research involved the histological recruitment and pathological verification of 178 UC patients and 356 age-/sex-matched controls without prior history of cancer. Arsenic species were determined by high-performance liquid chromatography (HPLC)-hydride generation and atomic absorption. 5-MedC levels were detected by HPLC and triple-quadrupole mass spectrometry (MS). 8-OHdG was processed by an online solid-phase extraction LC-MS/MS. Plasma folate levels were measured using the chemiluminescent technology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multiple logistic regression analysis. Results indicate that the high levels of total urinary arsenic, inorganic arsenic percentage, and 8-OHdG and the low levels of DMA % and plasma folate were independent factors of UC. In addition, global 5-MedC levels in the first quartile versus fifth quartile significantly increased the twofold OR of UC after potential factors were adjusted (95% CI:1.10-4.03). The interaction of 5-MedC level and high total arsenic level, insufficient arsenic capacity, high 8-OHdG, and low folate levels was insignificant. Results of stepwise logistic regression analysis indicate that high total urinary arsenic levels (Q3 versus Q1), low plasma folate level, and low global 5-MedC (Q4 versus Q5) significantly increased the ORs of UC. The above results suggest that high total arsenic, low plasma folate, and 5-MedC levels affect the ORs of UC independently.
环境砷暴露可能与 DNA 低甲基化的紊乱有关。本研究旨在首次探讨尿总砷水平、砷甲基化能力、8-羟基-2'-脱氧鸟苷（8-OHdG）、血浆叶酸和全球 5-甲基-2'-脱氧胞苷（5-MedC）水平的相互作用对尿路上皮癌（UC）风险的影响。构建了一项基于医院的病例对照研究。该研究包括组织学招募和 178 例 UC 患者和 356 例年龄/性别匹配的无癌症既往史对照患者的病理验证。砷形态通过高效液相色谱（HPLC）-氢化物发生和原子吸收法测定。5-MedC 水平通过 HPLC 和三重四极杆质谱（MS）检测。8-OHdG 通过在线固相萃取 LC-MS/MS 处理。使用化学发光技术测量血浆叶酸水平。通过多因素逻辑回归分析计算比值比（OR）和 95%置信区间（CI）。结果表明，尿总砷、无机砷百分比和 8-OHdG 水平较高，DMA%和血浆叶酸水平较低是 UC 的独立因素。此外，在调整潜在因素后，第一四分位和第五四分位的全球 5-MedC 水平显著增加了 UC 的两倍 OR（95%CI：1.10-4.03）。5-MedC 水平与高总砷水平、砷能力不足、高 8-OHdG 和低叶酸水平之间的相互作用不显著。逐步逻辑回归分析的结果表明，高尿总砷水平（Q3 与 Q1）、低血浆叶酸水平和低全球 5-MedC（Q4 与 Q5）显著增加了 UC 的 OR。上述结果表明，高总砷、低血浆叶酸和 5-MedC 水平独立影响 UC 的 OR。
