Molecular Markers in Sex Hormone Pathway Genes Associated with the Efficacy of Androgen-Deprivation Therapy for Prostate Cancer
Journal
PLoS ONE
Journal Volume
8
Journal Issue
1
Pages
e54627
Date Issued
2013
Author(s)
Yu C.-C.
Huang S.-P.
Lee Y.-C.
Liu C.-C.
Hour T.-C.
Huang C.-N.
You B.-J.
Chang T.-Y.
Huang C.-H.
Bao B.-Y.
Abstract
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. ? 2013 Yu et al.
SDGs
Other Subjects
androgen receptor; aromatase; sex hormone; aged; AKR1C3; androgen deprivation therapy; androgen metabolism; androgen receptor gene; article; CAG repeat; cancer mortality; cancer specific survival; cancer survival; cohort analysis; controlled study; CYP19A1 gene; estrogen metabolism; gene; gene identification; gene locus; genetic association; genetic marker; genetic risk; genetic variability; genotype; human; major clinical study; male; prostate cancer; risk assessment; signal transduction; single nucleotide polymorphism; survival time; Aged; Androgen Antagonists; Genetic Markers; Gonadal Steroid Hormones; Humans; Male; Multivariate Analysis; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Risk Factors
Type
journal article