UDP-glucuronosyltransferases and biochemical recurrence in prostate cancer progression.

BMC Cancer 2017 Jul 3;17(1):463. Epub 2017 Jul 3.

Cedars-Sinai Health System, Center for Integrated Research on Cancer and Lifestyle, Cancer Genetics and Prevention Program, Surgery, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.

Background: Uridine 5'-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal tissue. The expression of the UGT2B15, UGT2B17, and UGT2B28 enzymes has not been evaluated in prostate tissue samples from hormone therapy-naïve patients.

Methods: We determined the expression of UGT2B15, UGT2B17, and UGT2B28 enzymes in 190 prostate tissue samples from surgical specimens of a multiethnic cohort of patients undergoing radical prostatectomy at the Durham Veterans Affairs Medical Center. The association between each protein's percent positive and H-score, a weighted score of staining intensity, and the risk of biochemical recurrence (BCR) was tested using separate Cox proportional hazards models. In an exploratory analysis, UGT2B17 total positive and H-score were divided at the median and we tested the association between UGT2B17 group and risk of BCR.

Results: The median follow-up for all patients was 118 months (IQR: 85-144). Of 190, 83 (44%) patients developed BCR. We found no association between UGT2B15 or UGT2B28 and risk of BCR. However, there was a trend for an association between UGT2B17 and BCR (HR = 1.01, 95% CI 1.00-1.02, p = 0.11), though not statistically significant. Upon further investigation, we found that patients with UGT2B17 higher levels of expression had a significant increased risk of BCR on univariable analysis (HR = 1.57, 95% CI 1.02-2.43, p = 0.041), although this association was attenuated in the multivariable model (HR = 1.50, 95% CI 0.94-2.40, p = 0.088).

Conclusions: Our findings suggest that UGT2B17 overexpression may be associated with a significant increased risk of BCR. These results are consistent with previous reports which showed UGT2B17 significantly expressed in advanced prostate cancer including prostate tumor metastases.

Download full-text PDF

http://dx.doi.org/10.1186/s12885-017-3463-6DOI Listing
July 2017

Publication Analysis

Top Keywords

risk bcr
positive h-score
ugt2b28 enzymes
increased risk
tissue samples
prostate cancer
ugt2b17 ugt2b28
ugt2b15 ugt2b17
biochemical recurrence
association ugt2b17
expression ugt2b15
prostate tissue
staining intensity
attenuated multivariable
trend association

Similar Publications

Epigenetic regulation of steroid inactivating UDP-glucuronosyltransferases by microRNAs in prostate cancer.

J Steroid Biochem Mol Biol 2016 Jan 15;155(Pt A):85-93. Epub 2015 Sep 15.

Pharmacogenomics Laboratory, Centre Hospitalier Universitaire (CHU) de Québec Research Center, and Faculty of Pharmacy, Laval University, G1V 4G2 Quebec, Canada. Electronic address:

Androgens play a central role in prostate cancer progression. Systemic and local androgen bioavailability is controlled by UDP-glucuronosyltransferases conjugating enzymes (UGT), namely UGT2B15, UGT2B17 and UGT2B28. Reporter vector assays in HEK293 cells initially validated in silico-predicted regulatory potential of candidate miRNAs to target UGT transcripts, including miR-376c, miR-409 and miR-494 for UGT2B17, miR-331-5p and miR-376c for UGT2B15 while none were efficient for UGT2B28. Read More

View Article and Full-Text PDF
January 2016

Genetic variations in UGT2B28, UGT2B17, UGT2B15 genes and the risk of prostate cancer: A case-control study.

Gene 2017 Nov 4;634:47-52. Epub 2017 Sep 4.

Reproductive Health Research Center (IRHRC) and Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Glucuronidation is a major pathway for elimination of exogenous and endogenous compounds such as environmental carcinogens and androgens from the body. This biochemical pathway is mediated by enzymes called uridine diphosphoglucuronosyltransferases (UGTs). Null (del/del) genes polymorphisms in UGT2B17, and UGT2B28 and D85Y single-nucleotide polymorphism (SNP) of UGT2B15 have been reported to increase the risk of prostate cancer. Read More

View Article and Full-Text PDF
November 2017

Characterization and regulation of UDP-glucuronosyltransferases in steroid target tissues.

J Steroid Biochem Mol Biol 1998 Apr;65(1-6):301-10

MRC Group in Molecular Endocrinology, CHUL Research Center and Laval University, Quebec, Canada.

Conjugation of compounds by glucuronidation is a pathway found in all vertebrates studied to date. Although, it is widely recognized that the liver is a major site of glucuronidation, it is now clear that extrahepatic tissues are also involved in the conjugation of compounds to which these tissues are exposed. High levels of androsterone glucuronide and androstane-3alpha,17beta-diol glucuronide found in the human prostate, breast cyst fluid and ovary follicular fluid suggest that glucuronidation of 5alpha-reduced C19 steroids occurs in these tissues. Read More

View Article and Full-Text PDF
April 1998

The UGT2B28 Sex-steroid Inactivation Pathway Is a Regulator of Steroidogenesis and Modifies the Risk of Prostate Cancer Progression.

Eur Urol 2016 Apr 26;69(4):601-609. Epub 2015 Jul 26.

Centre Hospitalier Universitaire de Québec Research Center, Faculty of Medicine, Laval University, Québec, Canada. Electronic address:

Background: Androgen inactivation occurs mainly through the glucuronidation conjugative reaction mediated by UDP-glucuronosyltransferases (UGTs). This metabolic process is involved in the control of systemic and local androgen bioavailability.

Objective: To examine the relationship among expression of the androgen-inactivating UGT2B28 enzyme, circulating steroid hormone levels, and clinical phenotype in prostate cancer (PCa). Read More

View Article and Full-Text PDF
April 2016