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Tissue Factor Pathway Inhibitor Gene Polymorphism -33T → C Predicts Improved Disease-Free Survival in Colorectal
A K Bazzarelli1, A S Scheer1, L H Tai2
1Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
Annals of Surgical Oncology
|March 13, 2016
Summary
The homozygous CC polymorphism in Tissue Factor Pathway Inhibitor (TFPI) is linked to better disease-free survival in colon cancer patients post-surgery. This genetic factor may offer protection against cancer recurrence, highlighting the coagulation system's role.
Area of Science:
- Oncology
- Genetics
- Hematology
Background:
- Tissue Factor Pathway Inhibitor (TFPI) is an anticoagulant with known antimetastatic properties.
- The homozygous CC polymorphism (-33T → C) of TFPI is associated with elevated TFPI levels and reduced risk of venous thromboembolism.
- This study investigates the impact of this TFPI polymorphism on disease-free survival (DFS) in cancer patients following curative resection.
Purpose of the Study:
- To evaluate the association between the TFPI -33T → C polymorphism and disease-free survival (DFS) in patients with colorectal cancer.
- To determine if the homozygous CC genotype of TFPI influences cancer recurrence rates after curative surgery.
- To explore the potential role of the coagulation system in cancer outcomes through genetic polymorphisms.
Main Methods:
- Analysis of prospectively collected clinical data and germline DNA from 127 colorectal cancer patients who underwent curative surgery.
- Genotyping of TFPI (-33T → C), factor V Leiden (G1691A), and prothrombin (G20210A) polymorphisms using polymerase chain reaction.
- Kaplan-Meier survival analysis and multivariable Cox proportional hazard regression to assess DFS and independent predictors.
Main Results:
- The CC genotype for TFPI was present in 11% of patients.
- Patients with the CC genotype showed a significantly superior DFS (HR 0.34, p=0.02) compared to TT/TC genotypes, with 5-year DFS of 63% vs. 24%.
- Multivariate analysis confirmed that the CC polymorphism was an independent predictor of improved DFS (HR 0.28, p=0.008).
Conclusions:
- The homozygous -33T → C TFPI polymorphism may confer a protective effect against colon cancer recurrence.
- These findings suggest a potential mediating role for the coagulation system in cancer patient outcomes.
- The inherited anticoagulant TFPI polymorphism could be a novel factor influencing cancer prognosis.
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