The protease activated receptor 1 gene variation IVSn -14A>T is associated with distant metastasis and cancer-specific survival in renal cell carcinoma

Abstract

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.

http://www.jurology.com/article/S0022-5347(13)03688-4/abstract