title: Tissue Factor Pathway Inhibitor Gene Polymorphism -33T → C Predicts Improved Disease-Free Survival in Colorectal Cancer.
abstract: Tissue factor pathway inhibitor (TFPI) is an anticoagulant with antimetastatic properties. The homozygous CC polymorphism of TFPI (-33T → C) is associated with higher TFPI levels and lower venous thromboembolism risk. This study was the first to evaluate the impact of this polymorphism on disease-free survival (DFS) in cancer patients after curative resection.
  
  
  
  A prospectively maintained tumor bank with clinical data was used to identify patients who underwent curative surgery for colorectal cancer between 1994 and 2006. Germline DNA was extracted from formalin-fixed, paraffin-embedded normal colonic mucosa. Single nucleotide polymorphisms for TFPI (-33T → C), factor V Leiden (G1691A), and prothrombin (G20210A) were determined by polymerase chain reaction. Survival analysis was described using the Kaplan-Meier method. Multivariable regression analysis was performed using the Cox proportional hazard model.
  
  
  
  Of the 127 patients identified, the CC genotype was found in 11 %. Venous thromboembolism incidence was 18 % in the TT/TC (wild type/heterozygous) genotypes and 7 % in the CC genotype (p = 0.46). The CC genotype was associated with superior DFS (hazard ratio 0.34, 95 % confidence interval 0.14-0.84; p = 0.02) with 5-year DFS of 63 vs. 24 % for CC vs. TT/TC, respectively. In multivariate analysis, CC polymorphism (hazard ratio 0.28, p = 0.008) was independently associated with improved DFS. The prevalence of factor V Leiden (0.8 %) and prothrombin (1.6 %) polymorphisms was too low to detect interaction with TFPI polymorphism or DFS.
  
  
  
  These findings indicate that the inherited anticoagulant homozygous -33T → C TFPI polymorphism may protect against colon cancer recurrence and suggests a mediating role for the coagulation system in cancer outcomes.
authors.affiliation: Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
authors.forename: A K
authors.initials: AK
authors.lastname: Bazzarelli
authors.affiliation: Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
authors.forename: A S
authors.initials: AS
authors.lastname: Scheer
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: L H
authors.initials: LH
authors.lastname: Tai
authors.affiliation: Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Seth
authors.affiliation: Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: C Tanese
authors.initials: CT
authors.lastname: de Souza
authors.affiliation: Methods Centre, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Petrcich
authors.affiliation: Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Jonker
authors.affiliation: Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Maroun
authors.affiliation: Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Carrier
authors.affiliation: Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada. rauer@ohri.ca.|Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Canada. rauer@ohri.ca.
authors.forename: R C
authors.initials: RC
authors.lastname: Auer
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor