The Association of Protease Activated Receptor 1 gene −506 I/D Polymorphism with Disease-Free Survival in Breast Cancer Patients

Abstract

Recent data have shown that tumor development and dissemination may be regulated by procoagulant/anticoagulant axis. The aim of the present study was to search for an association of the protease activated receptor (PAR)1 gene -506 insertion/deletion (I/D), factor V Leiden (FVL), prothrombin (PT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with disease-free survival (DFS) in breast cancer. Genotyping of -506 I/D in the promoter region of PAR1 gene was performed by single-strand conformation polymorphism analysis and sequencing. FVL, PT G20210A, and MTHFR C677T were also determined by the method of polymerase chain reaction-based DNA analysis. Data regarding patient's age, menopausal status, tumor size, lymph node status, disease stage, tumor grade, estrogen and progesterone receptor, c-erb B2 expression, PAR1 -506 I/D, MTHFR C677T, FVL, and PT G20210A polymorphisms were examined by the univariate and multivariate analyses. Recurrent disease occurred in 29 patients (19.6 %) within a median of 20 months. It was found that tumor size, lymph node status, tumor stage, tumor grade, c-erbB2 expression, and PAR1 -506 I/D polymorphism were associated with DFS when Kaplan-Meier method was applied (P<.05). By Cox proportional hazards model, the presence of allele D at -506 locus (P=.0249) and small tumor size (P=.0001) were significant favorable prognostic factor, but c-erbB2 expression was an adverse prognostic factor (P=.0049). Our study suggested the protective effect of the allele D at -506 locus of PAR1 gene on the recurrence of breast cancer.