Genetic polymorphisms in androgen receptor-binding sites predict survival in prostate cancer patients receiving androgen-deprivation therapy
Journal
Annals of Oncology
Journal Volume
23
Journal Issue
3
Pages
707-713
Date Issued
2012
Author(s)
Huang C.-N.
Huang S.-P.
Pao J.-B.
Chang T.-Y.
Lan Y.-H.
Lu T.-L.
Lee H.-Z.
Juang S.-H.
Wu P.-P.
Hsieh C.-J.
Bao B.-Y.
Abstract
Background: Activated androgen receptor binds to androgen-responsive elements (AREs) in genome to regulate target gene transcription and, consequently, mediates physiological or tumorigenic processes of the prostate. Our aim was to determine whether genetic variants in AREs are associated with clinical outcomes after androgen-deprivation therapy (ADT) in prostate cancer patients. Patients and methods: We systematically investigated 55 common single-nucleotide polymorphisms (SNPs) in the genome-wide insilico-predicted AREs in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed by Kaplan-Meier analysis and Cox regression model. Results: In univariate analysis, two, five, and four SNPs were associated with disease progression, PCSM, and ACM, respectively. After adjusting for known prognostic factors, ARRDC3 rs2939244, FLT1 rs9508016, and SKAP1 rs6504145 remained as significant predictors for PCSM and FBXO32 rs7830622 and FLT1 rs9508016 remained as significant predictors for ACM in multivariate analysis. Moreover, strong combined genotype effects on PCSM and ACM were also observed (P trend < 0.001). Conclusion: Our results suggest that SNPs in AREs influence prostate cancer survival and may further advance our understanding of the disease progression. ? The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Subjects
Androgen-; Androgen-deprivation therapy; Nucleotide polymorphism; Prostate cancer; Responsive element; Single-
SDGs
Other Subjects
androgen receptor; antiandrogen; gonadorelin agonist; advanced cancer; aged; androgen deprivation therapy; ARRDC3 gene; article; binding site; cancer growth; cancer mortality; cancer patient; cancer radiotherapy; cancer survival; cohort analysis; computer model; controlled study; FBXO32 gene; FLT1 gene; gene; genetic association; genetic variability; genotype; hormone responsive element; human; major clinical study; male; orchiectomy; prediction; priority journal; prognosis; prospective study; prostate cancer; prostatectomy; single nucleotide polymorphism; SKAP1 gene; Aged; Androgen Antagonists; Arrestins; Genotype; Humans; Kaplan-Meier Estimate; Male; Neoplasm Staging; Phosphoproteins; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Receptors, Androgen; Response Elements; Vascular Endothelial Growth Factor Receptor-1
Type
journal article