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

Abstract

Purpose: PAR-1 mediates angiogenesis and impacts the process of tumor growth and disease progression. We evaluated the associations of the gene variations PAR-1 IVSn -14 A>T (rs168753), -506 Ins/Del (rs11267092) and -1426 C>T (rs32934) with renal cell carcinoma pathology and cancer specific survival.

Materials and methods: DNA was extracted from the peripheral blood leukocytes of 236 consecutive patients with renal cell carcinoma. Genotyping was done using restriction fragment length polymorphism analysis of polymerase chain reaction 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, cancer specific survival of patients with IVSn -14 AA was significantly worse than in those with AT/TT (HR 2.98, p = 0.019). The 1 and 4-year cancer specific survival 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 on multivariable analysis, IVSn -14 AA was identified as an independent adverse prognostic factor (HR 2.72, p = 0.044). The variations -506 Ins/Del and -1426 C>T were not significantly associated with pathological factors or cancer specific survival.

Conclusions: Results suggest that the AA genotype of the PAR-1 variation IVSn -14 A>T is associated with an increased risk of metastasis and poorer prognosis of renal cell carcinoma. Therefore, assessing the individual risk based on genotypes may be a helpful adjunct to identify subgroups at high risk for a poor clinical outcome.

Keywords: A; C; CSS; D; G; I; IVSn; PAR; PAR-1; PCR; RCC; SNP; T; VEGF; adenine; cancer specific survival; carcinoma; cytosine; deletion; guanine; insertion; intervening sequence; kidney; neoplasm metastasis; polymerase chain reaction; polymorphism; protease activated receptor; receptor; renal cell; renal cell carcinoma; single nucleotide; single nucleotide polymorphism; thymine; vascular endothelial growth factor.