SIGNIFICANCE OF THE T-34C POLYMORPHISM IN THE CYP17A1 GENE IN THE DEVELOPMENT OF BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER

Resume. Androgens play an important role during the development of both normal prostate epithelium and prostate cancer and variants of genes involved in androgen metabolism may be related to an increased risk of prostate disease. Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a key regulatory enzyme in the steroidogenic pathway; it catalysis both 17α-hydroxylase and 17,20-lyase activities and is essential for the production of both androgens and glucocorticoids. In this review, we focus on the structure and enzymatic activity of CYP17A1 and the mechanism of modulation of CYP17A1 activities. We discuss the relationship between common genetic variations in CYP17A1 gene and prostate cancer risk and the main effects of these variations on the prediction of susceptibility and clinical outcomes of prostate cancer patients. The mechanism of action, the efficacy and the clinical potential of CYP17A1 inhibitors in prostate cancer are also summarized. Keywords: CYP17A1, Steroid 17 alpha-hydroxylase/17,20-lyase, CYP17A1 polymorphisms, CYP17A1 inhibitors, prostate cancer.

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