Division of Nephrology and Kidney Institute, Department of Internal Medicine, China Medical University and Hospitals, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; Division of Nephrology, Asia University Hospital, Taichung, Taiwan; Department of Post-baccalaureate Veterinary Medicine, Asia University, Taichung, Taiwan.
Division of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan.
Chemosphere. 2021 Jun;273:127834. doi: 10.1016/j.chemosphere.2020.127834. Epub 2020 Sep 3.
Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalates and is associated with breast cancer. Ths association between DEHP and other types of cancer is not clear. DEHP may increase matrix metalloproteinase-9 that is critical for the development of urothelial cancer (UC). We examined the association between urinary phthalate metabolites and UC. CKD patients were selected as a control group because CKD patients are more at risk of UC than the general population.
In this cross-sectional study, we measured seven urinary phthalate metabolites that are abundant and can be measured using HPLC-MS/MS in Taiwan CKD patients between Jul 2013 and Dec 2015. MiBP (a urinary metabolite of Dibutyl phthalates[DBP]) and MEHHP (a urinary metabolite of DEHP) were described because they are the most abundant phthalate metabolites. The association of phthalate (log-transformed) and UC were analyzed using logistic regression with adjustments for age, gender, renal function, use of traditional Chinese medicine, toxins (dye, organic solvent), and non-steroidal anti-inflammatory drugs.
We measured the urinary MEHHP and MiBP of 496 patients (224 UC and 272 CKD patients). The urinary MEHHP was associated with UC but MiBP was not. Medical history including the use of non-steroid anti-inflammatory drugs, exposure to environmental toxins (dye, paint, and organic solvent), and the use of traditional Chinese medicine was independently associated with UC. The adjusted odds ratio of MEHHP was 1.42 (95% confidence interval: 1.21-1.68).
Phthalate urinary metabolite(MEHHP) may be associated with UC in CKD patients and the association is independent of well-known risk factors of UC.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是最广泛使用的邻苯二甲酸酯之一，与乳腺癌有关。DEHP 与其他类型癌症之间的关系尚不清楚。DEHP 可能会增加基质金属蛋白酶-9，这对膀胱癌（UC）的发展至关重要。我们研究了尿邻苯二甲酸酯代谢物与 UC 之间的关系。选择慢性肾脏病（CKD）患者作为对照组，因为 CKD 患者比一般人群更易患 UC。
在这项横断面研究中，我们测量了 7 种尿邻苯二甲酸代谢物，这些代谢物在台湾 CKD 患者中含量丰富，可使用 HPLC-MS/MS 进行测量。MiBP（邻苯二甲酸二丁酯[DBP]的尿代谢物）和 MEHHP（DEHP 的尿代谢物）被描述，因为它们是最丰富的邻苯二甲酸代谢物。使用逻辑回归分析调整年龄、性别、肾功能、使用中药、毒素（染料、有机溶剂）和非甾体抗炎药后，分析了邻苯二甲酸（对数转换）与 UC 的关系。
我们测量了 496 名患者（224 名 UC 患者和 272 名 CKD 患者）的尿 MEHHP 和 MiBP。尿 MEHHP 与 UC 相关，但 MiBP 则不然。包括使用非甾体抗炎药、暴露于环境毒素（染料、油漆和有机溶剂）以及使用中药在内的病史与 UC 独立相关。MEHHP 的调整后比值比为 1.42（95%置信区间：1.21-1.68）。
在 CKD 患者中，邻苯二甲酸尿代谢物（MEHHP）可能与 UC 相关，且这种关联独立于 UC 的已知危险因素。
