Association of SRD5A2 Genotype and Pathological Characteristics of Prostate Tumors

PI: Timothy Rebbeck
University of Pennsylvania

Background: Androgen metabolism genes are thought to play a role in the development of prostate cancer. One such gene, SRD5A2, encodes for 5"-reductase type II, an enzyme that converts testosterone to a more metabolically active metabolite dihydrotestosterone (DHT). DHT has more androgen activity in the prostate than testosterone and when it is bound to the androgen receptor it activates genes involved in prostate development and growth. Therefore, SRD5A2 may be involved in prostate cancer development. These investigators studied the A49T and V89L polymorphisms or variants of SRD5A2 in prostate tumors removed from men. The presence of the A49T polymorphism was associated with several indicators of poor prognosis including advanced disease and greatly increased prostate specific antigen levels. These results suggest that the A49T mutation may affect the severity of prostate cancer and thus be a predictor of patient outcome.

Citation: J.M. Jaffe, S.B. Malkowicz, A. H. Walker, S. MacBride, R. Peschel, J. Tomaszewski, K. Van Arsdalen, A.J. Wein, T.R. Rebbeck. Cancer Research,60(6):1626-30.