Factor V Leiden and prothrombin G20210A polymorphisms are not associated with disease-free survival in breast cancer

Abstract

It is known that cancer and its treatment can induce a hypercoagulable state. On the other hand, coagulation and fibrinolysis can play a significant role in tumor growth, invasion, dissemination and metastasis [1].The significant presence of factor V Leiden (FVL) and/or prothrombin (PT) G20210A polymorphisms which are the two most common defects in Caucasians are responsible for coagulation abnormality in thrombophilia. A few previous reports investigated the relationship between the cancer development and FVL and PT G20210A polymorphisms and found no association of FVL and some types of cancer [2–6]. On the contrary, Pihusch and coworkers demonstrated that the prevalence of PT G20210A polymorphism was significantly increased in patients with gastrointestinal carcinoma as compared to normal subjects [7]. However the role of FVL and PT G20210A polymorphisms in the recurrence risk and prognosis of breast cancer has not been investigated yet. We have read with great interest in the recent publications about experimental metastasis model in FVLdeficient mice [8, 9]. Bruggeman et al. showed that mice carrying FVL mutation were more susceptible to cancer cell metastasis after the injection of melanoma cells into the tail vein [8]. But, other study by Klerk et al. indicated that FVL mutation had no effect on the metastasis of colon cancer to the livers of mice [9]. Encouraged by the reports, we have retrieved data in 123 operable breast cancer and performed an analysis to investigate the role of FVL and PT G20210A polymorphisms in the recurrence (loco-regional and/or distant recurrence) of breast cancer. Genomic DNA isolation was performed from peripheral venous blood by standard phenol-chlorophorm extraction and FVL and PT G20210A polymorphisms were determined by using commercially available LightCycler kits (Roche Diagnostic, Roche Molecular Biochemicals, Mannheim, Germany) [10]. Data regarding patient’s age, tumor type, tumor size, lymph node status, tumor stage, grade, estrogen and progesterone receptor, c-erb B2 expression, FVL and PT G20210A polymorphisms were examined by univariate and multivariate analyses. The Kaplan Meier method was applied to examine the effect of individual variables on disease free survival (DFS). The significance of the observed difference between groups was calculated by the logrank test. The combined and independent effects of the factors on DFS were examined using the Cox proportional hazards model. Statistical analysis was done using SPSS 13.0 for Windows. For all test, a P value of less than 0.05 was considered to be significant. The follow-up period ranged from 4 to 216 months (mean, 57 months). Recurrent disease occurred in 22 patients within a mean time of 26 months (range: 6– 72 months). The univariate analysis factors having significant effects on DFS were tumor size, lymph node status, tumor stage, and c-erb B2 expression (P \ 0.05). FVL was detected in 10 breast cancer patients and the recurrent disease was developed in three of them. As shown in Fig. 1, the 5-year DFS rate in patients with FVL mutation was lower than those without FVL (68% vs. 82%), however this difference did not reach statistically significant A. Eroglu (&) R. Cam Department of General Surgery, Ankara University Medical School, Ankara, Turkey e-mail: aydaneroglu@hotmail.com