Abstract
Prostate cancer is a very common disease in more developed countries, but its cause is largely unknown. It is an androgen-dependent cancer, and it has been proposed that variations in androgen metabolism may affect a man’s risk of this disease [1]. There is accumulating evidence that increased intraprostatic androgen metabolism, particularly through the enzyme steroid 5α-reductase, may have an important role in predisposition to prostate cancer [2]. This enzyme catalyses the conversion of testosterone to dihydrotestosterone — the most potent androgen in the prostate. Thus, genetic variants encoded by the steroid 5α-reductase gene (SRD5A2) may affect the risk of developing prostate cancer. Makridakis et al. recently reported a missense mutation in SRD5A2, which results in the replacement of an alanine residue at codon 49 with threonine (A49T) [3]. This A49T amino acid substitution increased the risk of clinically significant disease 7.2-fold in African-American men and 3.6-fold in Hispanic men. This clinical association is further supported by data obtained in vitro showing that the mutant enzyme had a higher enzymatic activity, indicating an increased metabolic activation of testosterone to dihydrotestosterone in carriers of the 49T allele. Furthermore, finasteride, a competitive inhibitor of SRD5A2, showed a much lower efficacy in inhibiting the enzymatic activity.
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References
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© 2002 Springer-Verlag Berlin Heidelberg
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Nauck, M., März, W., Wieland, H. (2002). Rapid Detection of Missense Mutations in the Prostatic Steroid 5α-Reductase Gene Using Real-Time Fluorescence PCR and Melting Curve Analysis. In: Dietmaier, W., Wittwer, C., Sivasubramanian, N. (eds) Rapid Cycle Real-Time PCR — Methods and Applications. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59397-0_14
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DOI: https://doi.org/10.1007/978-3-642-59397-0_14
Publisher Name: Springer, Berlin, Heidelberg
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