Background

The progression of endometrial cancer (EC) is closely related to estrogen levels. UDP-glucuronosyltransferases (UGTs) are an essential class of phase II metabolizing enzymes that play a pivotal role in detoxifying steroid hormone.

Purpose

In this study, we aimed to uncover the role of UGTs in estrogen metabolism and the pathogenesis of EC.

Methods

A total of 100 unrelated EC patients (mean age 52.15 ± 10.04 y) and 100 healthy subjects (mean age 50.26 ± 8.80 y) were recruited for analysis of the UGT gene polymorphism and estrogen level. In six cases of EC, EC-adjacent tissues and cancer tissues were collected for detection of UGT expression.

Results

Our results showed that the estrogen homeostasis profile was disturbed in EC patients, with carcinogenic catechol estrogens (4-OHE1, 2-OHE1, 2-OHE2) significantly accumulated in the serum of these patients. Also, levels of estrogen-glucuronides were decreased significantly, and the expression of UGT1A8 and UGT2B7 in uterine tissues was downregulated in EC patients. Consistent with this, we observed that the distribution of genotypes and allele frequencies in UGT1A8 rs1042597 and UGT2B7 rs7439366 was significantly different between EC patients and healthy volunteers.

Conclusion

These results indicated that UGT1A8 and UGT2B7 may contribute to the estrogen signaling pathway and the pathogenesis of EC.

中文翻译：

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子宫UDP-葡糖醛酸糖基转移酶1A8（UGT1A8）和UDP-葡糖醛酸糖基转移酶2B7（UGT2B7）的功能涉及基于雌激素代谢调节的子宫内膜癌。

背景

子宫内膜癌（EC）的进展与雌激素水平密切相关。UDP-葡萄糖醛酸糖基转移酶（UGT）是II期代谢酶的必不可少的一类，在类固醇激素排毒中起关键作用。

目的

在这项研究中，我们旨在揭示UGTs在雌激素代谢和EC发病机理中的作用。

方法

总共招募了100名无关的EC患者（平均年龄52.15±10.04 y）和100名健康受试者（平均年龄50.26±8.80y）用于分析UGT基因多态性和雌激素水平。在六例EC中，收集EC相邻组织和癌组织用于检测UGT表达。

结果

我们的结果表明，EC患者的雌激素稳态分布受到干扰，致癌儿茶酚雌激素（4-OHE1、2-OHE1、2-OHE2）在这些患者的血清中大量积累。而且，EC患者子宫内组织中的雌激素-葡糖醛酸苷水平显着降低，UGT1A8和UGT2B7的表达下调。与此相符，我们观察到EC患者和健康志愿者在UGT1A8 rs1042597和UGT2B7 rs7439366中的基因型和等位基因频率的分布存在显着差异。

结论

这些结果表明UGT1A8和UGT2B7可能有助于雌激素信号通路和EC的发病机制。