Personalized Treatment of Prostate Cancer Based on Inherited Variations of Steroid Pathway–Related Genes

Abstract

There is increasing evidence that genetic differences of genes involved in the synthesis and biotransformation of steroid hormones are independent predictors of outcome in prostate cancer (PCa). In this issue, Audet-Walsh and colleagues report that specific single nucleotide polymorphisms (SNPs) in the family of hydroxysteroid (17-beta) dehydrogenase (HSD17B) genes are associated with increased risk for biochemical recurrence in localized PCa [1]. Furthermore, they demonstrate that various SNPs predict decreased progression-free and overall survival in advanced PCa. The possibility of characterizing the complete DNA of a human being within several days led to the initiation of large human genomewide association studies that focused mainly on the identification of genes potentially associated with the development of PCa. In several studies, common variants of chromosome 8q24 could be identified as associated with an increased risk for PCa [2]. In addition to these large studies performing complete DNA characterization of individuals, an increasing number of studies have characterized genetic variations of selective genes encoding for proteins involved in the development and progression of PCa. These studies not only focused on gene variants associated with an increased risk for developing PCa but also investigated whether variations of genes exist that predict poor outcome in PCa patients. The androgen receptor pathway has been identified as a main contributor to the pathobiology and aggressiveness of PCa. We have used the knowledge about the role of androgens as a stimulus for PCa growth for a long time to treat patients with advanced disease by suppressing systemic androgen levels. However, a considerable propor-