Association of genetic variants in VEGF-A with clinical recurrence in prostate cancer patients treated with definitive radiotherapy

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• 作者：T. Langsenlehner M.D. (1)
  E.-M. Thurner (1)
  W. Renner (2)
  A. Gerger (3)
  K.S. Kapp (1)
  U. Langsenlehner (4)
  
• 关键词：Prostate neoplasms ; Neoplasm recurrence ; local ; Prognosis ; Vascular endothelial growth factor ; A ; Genotypes ; Prostataneoplasien ; Lokales Neoplasierezidiv ; Prognose ; Vaskul?rer endothelialer Wachstumsfaktor A ; Genotypen
• 刊名：Strahlentherapie und Onkologie
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：190
• 期：4
• 页码：364-369
• 全文大小：520 KB
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• 作者单位：T. Langsenlehner M.D. (1)
  E.-M. Thurner (1)
  W. Renner (2)
  A. Gerger (3)
  K.S. Kapp (1)
  U. Langsenlehner (4)
  
  1. Department of Therapeutic Radiology and Oncology, Medical University of Graz, Auenbruggerplatz 32, 8036, Graz, Austria
  2. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
  3. Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
  4. Division of Internal Medicine, GKK Outpatient Department, Graz, Austria
  
• ISSN：1439-099X

文摘

Background and purpose Vascular endothelial growth factor-A (VEGF-A), a key regulator of tumor-induced angiogenesis, is critical for tumor growth and metastasization. The goal of the present study was to evaluate the prognostic value of VEGF single nucleotide polymorphisms (SNPs) and haplotypes for clinical recurrence after definitive radiotherapy for prostate cancer. Patients and methods The association of seven VEGF-A polymorphisms and their haplotypes with clinical recurrence (defined as the occurrence of local recurrence and/or distant metastases) in 496?prostate cancer patients treated with definitive radiotherapy were investigated. Genotypes were determined by 5-nuclease (TaqMan) assays; haplotypes were analyzed using the Haploview program. Results Within a median follow-up time of 80?months, 44?patients (9-) developed clinical recurrences. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms (?-578C > A, ?-489C > T, ?-498C > T, ?-34G > C, ?-C > T) upstream of the coding sequence (CCCCC, ATTGC, CCCGC, ATTGT) and two polymorphisms (936C > T, 1612G > A) downstream of the coding sequence (CA, CG, TG). Carriers of at least 1?copy of the ATTGC haplotype were at higher risk of recurrence (hazard ratio [HR] 3.83; 95-CI 1.48-.90, p--.006); for carriers of 2?copies, the HR was 4.85 (95-CI 1.72-3.6; p--.003). In multivariate analysis, patients harboring at least one copy of the ATTGC haplotype remained at increased risk of recurrence (HR 3.63, 95-CI 1.38-.55, p--.009); in patients carrying 2?copies, the HR was 4.72 (95-CI 1.64-3.6, p--.004). Conclusion Our findings indicate that the VEGF-A ATTGC haplotype may predict clinical recurrence in prostate cancer patients treated with radiotherapy.