Low-Activity V89L Variant in SRD5A2 Is Associated with Aggressive Prostate Cancer Risk: An Explanation for the Adverse Effects Observed in Chemoprevention Trials Using 5-Alpha-Reductase Inhibitors

2007 ◽  
Vol 52 (4) ◽  
pp. 1082-1089 ◽  
Author(s):  
Olivier Cussenot ◽  
Abdel-Rahmène Azzouzi ◽  
Nathalie Nicolaiew ◽  
Philippe Mangin ◽  
Luc Cormier ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Adverse Effects ◽  
Prostate Cancer Risk ◽  
Aggressive Prostate Cancer ◽  
Reductase Inhibitors ◽  
5 Alpha Reductase Inhibitors ◽  
Low Activity

The Case for Prostate Cancer Risk Reduction by 5-Alpha Reductase Inhibitors

2012 ◽  
pp. 92-95
Author(s):  
Youssef S. Tanagho ◽  
Gerald L. Andriole
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Risk Reduction ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Public Health Problem ◽  
High Grade ◽  
Reductase Inhibitors ◽  
5 Alpha Reductase Inhibitors ◽  
Cancer Risk Reduction

Overview: Prostate cancer remains a significant public health problem. The current approach with prostate-specific antigen (PSA)-based screening has questionable effects on prostate cancer–specific mortality but is clearly associated with overdiagnosis of prostate cancer, especially relatively low-risk and low-volume tumors. Methods to decrease overdiagnosis include alterations in screening practices and, potentially, the use of 5-alpha reductase inhibitors. This article reviews the major trials that have evaluated 5-alpha reductase inhibitors in this setting: the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride Prostate Cancer Events Trial (REDUCE). Although these trials enrolled different patient populations, their findings are complementary and suggest a potential role for these agents in prostate cancer risk reduction. Use of 5-alpha reductase inhibitors results in an approximate 25% reduction in the detection of prostate cancer, reduces diagnosis of high-grade prostatic intraepithelial neoplasia (PIN), and improves benign prostatic hyperplasia (BPH)-related outcomes and the performance of PSA as a diagnostic test for aggressive prostate cancer. Side effects occur in a small percentage of men and consist of decreased sexual function and libido as well as gynecomastia. The risk of high-grade tumor development while receiving these agents is uncertain.

scholarly journals Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian-randomization study based on 79 148 prostate-cancer cases and 61 106 controls

2019 ◽  
Vol 49 (2) ◽  
pp. 587-596 ◽  
Author(s):  
Nabila Kazmi ◽  
Philip Haycock ◽  
Konstantinos Tsilidis ◽  
Brigid M Lynch ◽  
Therese Truong ◽  
...  
Keyword(s):  
Physical Activity ◽  
Prostate Cancer ◽  
Risk Factors ◽  
Cancer Risk ◽  
Serum Iron ◽  
Mendelian Randomization ◽  
Prostate Cancer Risk ◽  
Uk Biobank ◽  
Monounsaturated Fat ◽  
Aggressive Prostate Cancer

Abstract Background Prostate cancer is the second most common male cancer worldwide, but there is substantial geographical variation, suggesting a potential role for modifiable risk factors in prostate carcinogenesis. Methods We identified previously reported prostate cancer risk factors from the World Cancer Research Fund (WCRF)’s systematic appraisal of the global evidence (2018). We assessed whether each identified risk factor was causally associated with risk of overall (79 148 cases and 61 106 controls) or aggressive (15 167 cases and 58 308 controls) prostate cancer using Mendelian randomization (MR) based on genome-wide association-study summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7844 prostate-cancer cases and 204 001 controls). Results WCRF identified 57 potential risk factors, of which 22 could be instrumented for MR analyses using single nucleotide polymorphisms. For overall prostate cancer, we identified evidence compatible with causality for the following risk factors (odds ratio [OR] per standard deviation increase; 95% confidence interval): accelerometer-measured physical activity, OR = 0.49 (0.33–0.72; P = 0.0003); serum iron, OR = 0.92 (0.86–0.98; P = 0.007); body mass index (BMI), OR = 0.90 (0.84–0.97; P = 0.003); and monounsaturated fat, OR = 1.11 (1.02–1.20; P = 0.02). Findings in our replication analyses in UK Biobank were compatible with our main analyses (albeit with wide confidence intervals). In MR analysis, height was positively associated with aggressive-prostate-cancer risk: OR = 1.07 (1.01–1.15; P = 0.03). Conclusions The results for physical activity, serum iron, BMI, monounsaturated fat and height are compatible with causality for prostate cancer. The results suggest that interventions aimed at increasing physical activity may reduce prostate-cancer risk, although interventions to change other risk factors may have negative consequences on other diseases.

scholarly journals Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer

2017 ◽  
Vol 35 (13) ◽  
pp. 1430-1436 ◽  
Author(s):  
Stacy Loeb ◽  
Yasin Folkvaljon ◽  
Jan-Erik Damber ◽  
Joseph Alukal ◽  
Mats Lambe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Replacement Therapy ◽  
Lower Risk ◽  
Conditional Logistic Regression ◽  
Prostate Cancer Risk ◽  
Testosterone Replacement ◽  
Testosterone Replacement Therapy ◽  
Aggressive Prostate Cancer ◽  
Risk Prostate Cancer

Purpose The association between exposure to testosterone replacement therapy (TRT) and prostate cancer risk is controversial. The objective was to examine this association through nationwide, population-based registry data. Methods We performed a nested case-control study in the National Prostate Cancer Register of Sweden, which includes all 38,570 prostate cancer cases diagnosed from 2009 to 2012, and 192,838 age-matched men free of prostate cancer. Multivariable conditional logistic regression was used to examine associations between TRT and risk of prostate cancer (overall, favorable, and aggressive). Results Two hundred eighty-four patients with prostate cancer (1%) and 1,378 control cases (1%) filled prescriptions for TRT. In multivariable analysis, no association was found between TRT and overall prostate cancer risk (odds ratio [OR], 1.03; 95% CI, 0.90 to 1.17). However, patients who received TRT had more favorable-risk prostate cancer (OR, 1.35; 95% CI, 1.16 to 1.56) and a lower risk of aggressive prostate cancer (OR, 0.50; 95% CI, 0.37 to 0.67). The increase in favorable-risk prostate cancer was already observed within the first year of TRT (OR, 1.61; 95% CI, 1.10 to 2.34), whereas the lower risk of aggressive disease was observed after > 1 year of TRT (OR, 0.44; 95% CI, 0.32 to 0.61). After adjusting for previous biopsy findings as an indicator of diagnostic activity, TRT remained significantly associated with more favorable-risk prostate cancer and lower risk of aggressive prostate cancer. Conclusion The early increase in favorable-risk prostate cancer among patients who received TRT suggests a detection bias, whereas the decrease in risk of aggressive prostate cancer is a novel finding that warrants further investigation.

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