Genetic polymorphisms in androgen receptor-binding sites predict survival in prostate cancer patients receiving androgen-deprivation therapy.
Ann Oncol
; 23(3): 707-713, 2012 Mar.
Article
in En
| MEDLINE
| ID: mdl-21652578
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 ANDMETHODS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoproteins
/
Prostatic Neoplasms
/
Receptors, Androgen
/
Arrestins
/
Polymorphism, Single Nucleotide
/
Vascular Endothelial Growth Factor Receptor-1
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Humans
/
Male
Language:
En
Journal:
Ann Oncol
Journal subject:
NEOPLASIAS
Year:
2012
Document type:
Article
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM