CYP17 T27C polymorphism and prostate cancer risk: a meta-analysis based on 31 studies

Objective：The cytochrome P450 17α-hydroxylase（CYP17）plays a vital role in androgen biosynthesis.A T-to-C polymorphism in the 5＇promoter region of CYP17 has been implicated as a risk factor for prostate cancer,but the results of individual studies are inconclusive or controversial.To derive a more precise estimation of the relationship,we performed an updated meta-analysis from 31 studies based on 27 publications.Methods：A comprehensive search was conducted to examine all the eligible studies of CYP17 polymorphism and prostate cancer risk.We used odds ratios（ORs）with 95%confidence intervals（CIs）to assess the strength of the association.Results：Overall,individuals with CC/CT genotype were not associated with prostate cancer risk （CC vs.TT：OR=1.03,95%CI=0.86-1.24,P=0.72,P heterogeneity 〈0.0001;CT vs.TT：OR=0.99,95%CI=0.87- 1.12,P=0.88,P heterogeneity =0.0006）.In the stratified analysis by ethnicity,there was a significantly increased risk of prostate cancer among individuals of African descent under the recessive model（OR=1.56,95%CI=1.01- 2.39,P=0.04,P heterogeneity =0.65）.Conclusion：This meta-analysis suggested that CYP17 polymorphism might be associated with prostate cancer risk among individuals of African descent.

UGT2B17 status and risk of prostate cancer: A meta-analysis

Objective: Recent studies on the association between Uridine diphosphoglucuronosyl tranferases (UGT) 2B17 status and risk of prostate cancer (PCa) showed inconclusive results. To clarify this possible association, we conducted a meta-analysis of published studies. Methods: We searched published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI). According to our inclusion criteria, studies that observed the association between UGT2B17 status and PCa risk were included. The principal outcome measure was the adjusted odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with UGT2B17 status. Results: A total of 6 studies with 7029 subjects (3839 cases and 3190 controls) were eligible for inclusion in the meta-analysis. Overall, there was a significant association between UGT2B17 status and increased risk of prostate cancer (OR = 1.74, 95% CI 1.14 - 2.64, P 0.001). Similar results were found in the subgroup analyses by ethnicity and types of controls. Conclusion: This meta-analysis demonstrates that UGT2B17 status is associated with prostate cancer susceptibility, and it contributes to increased risk of prostate cancer.

Androgen-AR axis in primary and metastatic prostate cancer: chasing steroidogenic enzymes for therapeutic intervention

Androgens play an important role in prostate cancer(PCa)development and progression.Although androgen deprivation therapy remains the front-line treatment for advanced prostate cancer,patients eventually relapse with the lethal form of the disease.The prostate tumor microenvironment is characterised by elevated tissue androgens that are capable of activating the androgen receptor(AR).Inhibiting the steroidogenic enzymes that play vital roles in the biosynthesis of testosterone(T)and dihydrotestosterone(DHT)seems to be an attractive strategy for PCa therapies.Emerging data suggest a role for the enzymes mediating pre-receptor control of T and DHT biosynthesis by alternative pathways in controlling intratumoral androgen levels,and thereby influencing PCa progression.This supports the idea for the development of multi-targeting strategies,involving both dual and multiple inhibitors of androgen-metabolising enzymes that are able to affect androgen synthesis and signalling at different points in the biosynthesis.In this review,we will focus on CYP17A1,AKR1C3,HSD17B3 and SRD5A,as these enzymes play essential roles in all the three androgenic pathways.We will review also the AR as an additional target for the design of bifunctional drugs.Targeting intracrine androgens and AKR1C3 have potential to overcome enzalutamide and abiraterone resistance and improve survival of advanced prostate cancer patients.