title: Thrombin-activatable fibrinolysis inhibitor Thr325Ile polymorphism and plasma level in breast cancer: A pilot study.
abstract: 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.
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Suez Canal University, Egypt.
authors.forename: Manal S
authors.initials: MS
authors.lastname: Fawzy
authors.affiliation: Histology (Genetic Unit) Department, Faculty of Medicine, Suez Canal University, Egypt.
authors.forename: Eman A
authors.initials: EA
authors.lastname: Mohammed
authors.affiliation: Clinical Pathology Department, Faculty of Medicine, Suez Canal University, Egypt.
authors.forename: Amal S
authors.initials: AS
authors.lastname: Ahmed
authors.affiliation: Clinical Pathology Department, Faculty of Medicine, Sohag University, Egypt.
authors.forename: Abeer
authors.initials: A
authors.lastname: Fakhr-Eldeen
keywords: ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; Ag, antigen; BC, breast cancer; Breast cancer; DIC, disseminated intravascular coagulopathy; ELISA, enzyme linked immunosorbent assay; ER, estrogen receptor; Egyptian; HER2, human epidermal growth factor receptor 2; IHPI, immunohistochemical prognostic index; NPI, nottingham prognostic index; NPP, normal pooled plasma; PR, progesterone receptor; PT, prothrombin time; SNP, single nucleotide polymorphism; TAFI, thrombin-activatable fibrinolysis inhibitor; TAFIa, activated TAFI; Thr325Ile polymorphism; Thrombin-activatable fibrinolysis inhibitor; VTE, vascular thromboembolic events; WBC, white blood cell