Molecular markers in sex hormone pathway genes associated with the efficacy of androgen-deprivation therapy for prostate cancer
Yu CC, Huang SP, Lee YC, Huang CY, Liu CC, Hour TC, Huang CN, You BJ, Chang TY, Huang CH, Bao BY. PLoS One. 2013;8(1):e54627. doi: 10.1371/journal.pone.0054627. Epub 2013 Jan 24.


Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan ; Department of Pharmacy, Tajen University, Pingtung, Taiwan ; School of Medicine, National Yang-Ming University, Taipei, Taiwan.


Although most advanced prostate cancer patients respond to androgen-deprivation therapy (ADT), the efficacy is widely variable. We investigated whether the host genetic variations in sex hormone pathway genes are associated with the efficacy of ADT. A cohort of 645 patients with advanced prostate cancer treated with ADT was genotyped for 18 polymorphisms across 12 key genes involved in androgen and estrogen metabolism. We found that after adjusting for known risk factors in multivariate Cox regression models, AKR1C3 rs12529 and AR-CAG repeat length remained significantly associated with prostate cancer-specific mortality (PCSM) after ADT (P≤0.041). Furthermore, individuals carrying two unfavorable genotypes at these loci presented a 13.7-fold increased risk of PCSM compared with individuals carrying zero (P<0.001). Our results identify two candidate molecular markers in key genes of androgen and estrogen pathways associated with PCSM after ADT, establishing the role of pharmacogenomics in this therapy.