Pharmacogenetics of human androgens and prostatic diseases.
Prostate cancer (PCa) and benign prostatic hypertrophy (BPH) are two common and growing public health problems in the Western world. We review here the recent biochemical and pharmacogenetic literature related to these two prostatic disorders. We focus first on constitutional ('germline') single nucleotide polymorphism (SNPs) at the steroid 5 alpha-reductase (SRD5A2) locus, which encodes the human prostatic (or Type II) steroid 5 alpha-reductase enzyme. The investigations reviewed point to several uses of personalised medicine at the SRD5A2 locus. In addition, we report on recent identification of somatic pharmacogenetic alterations at the androgen receptor (AR) locus, which encodes the human androgen receptor, suggesting that this also may be a fruitful field of investigation, with important clinical applications. Pharmacogenomic investigation of constitutional and somatic DNA changes in human genes predisposing to cancer may lead to significant advances in chemoprevention, presymptomatic diagnosis and improved treatment of PCa.
Novelli
G
G
Dipartimento di Biopatologia e Diagnostica per Immagini, Università di Roma Tor Vergata, 00133 Roma, Italy. novelli@med.uniroma2.it
Margiotti
K
K
Sangiuolo
F
F
Reichardt
J K
JK
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D018120:Finasteride / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism
D011944:Receptors, Androgen; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase