Archives of Toxicology

, Volume 88, Issue 4, pp 901–911

Genetic variations in TP53 binding sites are predictors of clinical outcomes in prostate cancer patients

Authors

  • Victor C. Lin
    • Department of UrologyE-Da Hospital
    • Department of NursingI-Shou University
  • Chao-Yuan Huang
    • Department of Urology, National Taiwan University Hospital, College of MedicineNational Taiwan University
  • Yung-Chin Lee
    • Department of UrologyKaohsiung Medical University Hospital
    • Department of Urology, Faculty of Medicine, College of MedicineKaohsiung Medical University
  • Chia-Cheng Yu
    • Division of Urology, Department of SurgeryKaohsiung Veterans General Hospital
    • Department of Urology, School of MedicineNational Yang-Ming University
    • Department of PharmacyTajen University
  • Ta-Yuan Chang
    • Department of Occupational Safety and HealthChina Medical University
  • Te-Ling Lu
    • Department of PharmacyChina Medical University
    • Department of UrologyKaohsiung Medical University Hospital
    • Department of Urology, Faculty of Medicine, College of MedicineKaohsiung Medical University
    • Department of PharmacyChina Medical University
    • Sex Hormone Research CenterChina Medical University Hospital
Toxicogenomics

DOI: 10.1007/s00204-014-1196-8

Cite this article as:
Lin, V.C., Huang, C., Lee, Y. et al. Arch Toxicol (2014) 88: 901. doi:10.1007/s00204-014-1196-8

Abstract

Since the tumor protein p53 (TP53), a transcription factor, plays a crucial role in prostate cancer development and progression, we hypothesized that sequence variants in TP53 binding sites might affect clinical outcomes in patients with prostate cancer. We systematically evaluated 41 single nucleotide polymorphisms (SNPs) within genome-wide predicted TP53 binding sites in a cohort of 1,024 prostate cancer patients. The associations of these SNPs with prostate cancer characteristics and clinical outcomes after radical prostatectomy for localized disease and after androgen-deprivation therapy (ADT) for advanced disease were assessed by Kaplan–Meier analysis and Cox regression model. ARAP2 rs1444377 and TRPS1 rs722740 were associated with advanced stage prostate cancer. FRK rs171866 remained as a significant predictor for disease progression; DAB2 rs268091 and EXOC4 rs1149558 remained as significant predictors for prostate cancer-specific mortality (PCSM); and EXOC4 rs1149558 remained as a significant predictor for all-cause mortality after ADT in multivariate models that included clinicopathologic predictors. In addition, the numbers of protective genotypes at DAB2 rs268091 and EXOC4 rs1149558 showed a cumulative effect on PCSM (P for trend = 0.002). Our results suggested that SNPs within TP53 binding sites might be valuable biomarkers for prostate cancer outcome prediction.

Keywords

MortalityPrognosisProstate cancerSingle nucleotide polymorphism (SNP)TP53Transcription factor binding sites

Abbreviations

SNP

Single nucleotide polymorphism

RP

Radical prostatectomy

ADT

Androgen-deprivation therapy

PCSM

Prostate cancer-specific mortality

ACM

All-cause mortality

PSA

Prostate-specific antigen

OR

Odds ratio

95 % CI

95 % confidence interval

HR

Hazard ratio

Supplementary material

204_2014_1196_MOESM1_ESM.doc (232 kb)
Supplementary material 1 (DOC 231 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014