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The Association of 5 Alpha Reductase Inhibitor Use and the Natural History of Bladder Cancer

Principal Investigator

Name
Michael Liss

Institution
University of Texas Health Science Center San Antonio

Position Title
Assistant Professor

Email
liss@uthscsa.edu

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
PLCO-110

Initial CDAS Request Approval
Oct 2, 2014

Title
The Association of 5 Alpha Reductase Inhibitor Use and the Natural History of Bladder Cancer

Summary
An estimated 74,560 new cases of bladder cancer can be expected to occur in 2014; of these, roughly half of patients present with non-muscle invasive (superficial) bladder cancer (NMIBC) (1). Of new bladder cancers diagnosed in the United States, by far the predominant histopathologic subtype is urothelial carcinoma (2). The bladder is an organ embryologically derived from the urogenital sinus; as such, it demonstrates expression of the androgen receptor transcription factor which may affect the tumorigenesis of urothelial carcinoma and epithelial to mesenchymal transition (EMT) and subsequent malignant transformation (3). The androgen receptor has been shown to be involved in recurrence and perhaps progression of NMIBC (4-5). As such, the potential exists to use androgen receptor expression to influence the variable natural history of bladder cancer (both muscle and non-muscle invasive disease) and possibly even affect progression and recurrence in these patients. One of the most potent androgens is dihydrotestosterone (DHT), a potently androgenic hormone synthesized by the action of the enzyme 5α-reductase in the cytosol of target tissues such as the prostate, sebaceous glands, and the urinary bladder. DHT has already been shown to affect bladder cancer cell line proliferation and differentiation in several urothelial cancer cell lines in vitro (6). Herein, we investigate the natural history of bladder cancer in men who are have or have not taken 5-ARI's in the context of a randomized cancer screening trial.

Aims

Specific Aim 1: To catalog and describe associations in the PLCO male cohort of men who subsequently developed bladder cancer and did or did not have any self-reported history of finasteride use.
Hypothesis 1: Self-reported history of finasteride usage altered the natural history of incident bladder cancer in the male PLCO cohort in some unknown manner.
Specific Aim 2: To determine if length of finasteride exposure is related to any change in bladder cancer incidence or mortality in PLCO participants.
Hypothesis 2: FInasteride use has a inverse dose-dependent effect on the incidence of aggressive bladder cancer and bladder cancer mortality in the PLCO male cohort.

Collaborators

Ian M. Thompson Jr. M.D.
Donna Ankerst Ph.D.
Edwin Morales M.D.

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