OBJECTIVE: Protease activated receptor 1 (PAR-1) mediates angiogenesis and impacts the process of tumor growth and disease progression.
The aim of this study was to evaluate the associations of the gene variations PAR-1 IVSn -14 A >T (rs168753), -506 Ins/Del (I/D) (rs11267092) and -1426 C >T (rs32934) with renal cell carcinoma (RCC) pathology and cancer-specific survival (CSS).
METHODS: DNA was extracted from peripheral blood leukocytes of 236 consecutive RCC patients. Genotyping was carried out using restriction fragment length polymorphism analysis of PCR amplicons and sequencing.
RESULTS: The IVSn -14 AA genotype was associated with a 3.13-fold increased risk of distant metastases (p=0.015). In addition, CSS of patients with IVSn -14 AA was significantly worse compared with AT/TT (HR 2.98, p=0.019). The 1- and 4-year CSS rate for AA vs. AT/TT was 89% vs. 99% and 82% vs. 92%, respectively. After adjusting for the stage, size, grade, and necrosis (SSIGN) score in the multivariable analysis, IVSn -14 AA (HR 2.72, p=0.044) was identified as an independent, adverse prognostic factor. The variations 506 I/D and -1426 C >T were not significantly associated with pathological factors and CSS.
CONCLUSION: The present study suggested that the AA genotype of the PAR-1 variation IVSn -14 A >T is associated with an increased risk of metastasis and poorer prognosis in RCC. The assessment of the individual risk on the basis of genotypes may therefore be a helpful adjunct to identify subgroups at high risk for poor clinical outcome.
Written by:
de Martino M, Haitel A, Schatzl G, Klatte T. Are you the author?
Department of Urology, Medical University of Vienna, Vienna, Austria.
Reference: J Urol. 2013 Mar 18. pii: S0022-5347(13)03688-4.
doi: 10.1016/j.juro.2013.03.041
PubMed Abstract
PMID: 23517743
UroToday.com Investigative Urology Section
