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

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• 作者：Victor C. Lin (1) (2)
  Chao-Yuan Huang (3)
  Yung-Chin Lee (4) (5)
  Chia-Cheng Yu (6) (7) (8)
  Ta-Yuan Chang (9)
  Te-Ling Lu (10)
  Shu-Pin Huang (4) (5)
  Bo-Ying Bao (10) (11)
  
• 关键词：Mortality ; Prognosis ; Prostate cancer ; Single nucleotide polymorphism (SNP) ; TP53 ; Transcription factor binding sites
• 刊名：Archives of Toxicology
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：88
• 期：4
• 页码：901-911
• 全文大小：360 KB
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• 作者单位：Victor C. Lin (1) (2)
  Chao-Yuan Huang (3)
  Yung-Chin Lee (4) (5)
  Chia-Cheng Yu (6) (7) (8)
  Ta-Yuan Chang (9)
  Te-Ling Lu (10)
  Shu-Pin Huang (4) (5)
  Bo-Ying Bao (10) (11)
  
  1. Department of Urology, E-Da Hospital, Kaohsiung, Taiwan
  2. Department of Nursing, I-Shou University, Kaohsiung, Taiwan
  3. Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
  4. Department of Urology, Kaohsiung Medical University Hospital, 100 Ziyou 1st Road, Kaohsiung, 807, Taiwan
  5. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  6. Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
  7. Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan
  8. Department of Pharmacy, Tajen University, Pingtung, Taiwan
  9. Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan
  10. Department of Pharmacy, China Medical University, 91 Xueshi Road, Taichung, 404, Taiwan
  11. Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan
  
• ISSN：1432-0738

文摘

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.