The function of uterine UDP-glucuronosyltransferase 1A8 (UGT1A8) and UDP-glucuronosyltransferase 2B7 (UGT2B7) is involved in endometrial cancer based on estrogen metabolism regulation.

Abstract

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. In this study, we aimed to uncover the role of UGTs in estrogen metabolism and the pathogenesis of EC. A total of 100 unrelated EC patients (mean age 52.15 ± 10.04y) and 100 healthy subjects (mean age 50.26 ± 8.80y) 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. 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. These results indicated that UGT1A8 and UGT2B7 may contribute to the estrogen signaling pathway and the pathogenesis of EC.