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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2016

01-07-2016 | Colorectal Cancer

Tissue Factor Pathway Inhibitor Gene Polymorphism −33T → C Predicts Improved Disease-Free Survival in Colorectal Cancer

Authors: A. K. Bazzarelli, MD, BScPT, A. S. Scheer, MD, MSc, L. H. Tai, PhD, R. Seth, MD, MSc, C. Tanese de Souza, DVet, W. Petrcich, MSc, D. J. Jonker, MD, J. A. Maroun, MD, M. Carrier, MD, R. C. Auer, MD, MSc

Published in: Annals of Surgical Oncology | Issue 7/2016

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
Tissue Factor Pathway Inhibitor Gene Polymorphism −33T → C Predicts Improved Disease-Free Survival in Colorectal Cancer
Authors
A. K. Bazzarelli, MD, BScPT
A. S. Scheer, MD, MSc
L. H. Tai, PhD
R. Seth, MD, MSc
C. Tanese de Souza, DVet
W. Petrcich, MSc
D. J. Jonker, MD
J. A. Maroun, MD
M. Carrier, MD
R. C. Auer, MD, MSc
Publication date
01-07-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 7/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5169-4

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