Role of PAI-1 and TAFI in the mediation of fibrinolytic deficit in cancer patients

Florian-Kujawski, M.; Hoppensteadt, Debra; Iqbal, Omar; Demir, Muzaffer; Tobu, M.; Fareed, D.; Fareed, Jawed

doi:10.1200/jco.2004.22.90140.9727

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“…Breast cancer patients showed a significant increase in their plasma TAFI levels, when compared with the control group; contributing to the fibrinolytic deficiency in these patients and reflecting their thrombotic state ( Chengwei et al, 2013 , Florian-Kujawski et al, 2004 , Kaftan et al, 2011 ). This finding runs in-line with disease progression, as the fibrin accumulation in the tumor could increase endothelial motility, worsen angiogenesis, and contribute to an increased risk of thrombosis in breast cancer patients ( Byrne et al, 2007 , Dirix et al, 2002 ).…”

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confidence: 95%

Thrombin-activatable fibrinolysis inhibitor Thr325Ile polymorphism and plasma level in breast cancer: A pilot study

et al. 2015

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This study aimed to investigate thrombin-activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphism and TAFI antigen (Ag) levels in breast cancer (BC) in the Egyptian population to clarify their role in relation to BC. A group of 300 females was recruited in this study; of these 150 unrelated patients with different stages of BC and 150 age-matched healthy controls. Plasma TAFI Ag was measured by ELISA and TAFI Thr325Ile (rs1926447) polymorphism was genotyped using TaqMan single nucleotide polymorphism (SNP) genotyping assay. The results showed the genotypes of the minor allele; Thr/Ile (CT) and Ile/Ile (TT) were significantly more frequent in patients compared to control group (50.0% and 22.0% vs. 42.0% and 13.3%, respectively) and were also associated with BC susceptibility [OR = 1.9 and 2.6; 95% CI: (1.1–3.3) and (1.3–5.5), respectively P = 0.01]. Ile325 allele carriers were more frequent in cases than in controls (47.0% vs. 34.0%) [OR = 1.7, (95% CI = 1.2–2.4), P = 0.001]. However, TAFI Thr325Ile polymorphism was not associated with BC stage or other clincopathological characteristics. TAFI Ag levels were correlated with advanced stages of BC, poor prognosis and risk of recurrence (P = 0.02, P = 0.04 and P < 0.001, respectively) and Thr325Ile SNP was significantly correlated with TAFI antigen levels with the C/C genotype corresponding to the highest and the T/T genotype to the lowest TAFI antigen levels (P < 0.001) in the study groups. In conclusion, this study showed for the first time that TAFI Thr325Ile polymorphism could have a contribution to BC susceptibility in our population. Furthermore, high TAFI plasma levels may serve as a predictor of poor prognosis in patients with BC.

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