Association of tissue factor pathway inhibitor gene polymorphism -33T→C with disease-free survival in colorectal cancer.
Bibliographic record
Abstract
395 Background: Tissue Factor Pathway Inhibitor (TFPI) is an anticoagulant protein exhibiting antimetastatic properties in preclinical models. The homozygous CC polymorphism on intron 7 of TFPI (-33T-->C) is associated with higher TFPI protein levels and a lower risk of venous thromboembolism (VTE). The present study is the first to evaluate the impact of the inherited TFPI polymorphism on disease-free survival (DFS) in cancer patients following curative resection. Methods: A prospectively maintained colorectal tumour bank with associated 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 (SNPs) for Tissue Factor Pathway Inhibitor (TFPI, -33T-->C), Factor V Leiden (FVL, G1691A), and Prothrombin (PT, G20210A) were determined by polymerase chain reaction. DFS was described using the Kaplan-Meier method. Multivariable regression analysis, with known prognostic factors, was performed using the Cox Proportional Hazard model. Results: Of the 139 patients identified, the prevalence of the wildtype (TT) TFPI genotype was found in 57.3% of samples, the heterozygous genotype (TC) in 29.4%, and the homozygous genotype (CC) in 10.5%. The incidence of VTE was 21.6% in the TT/TC genotypes and 6.7% in the CC genotype (p=0.4). The CC genotype was associated with superior DFS (HR 0.38, [95%CI 0.17-0.88]; p=.02) with 5 year DFS 56.3% vs. 24.6% for CC vs. TT/TC respectively. In multivariate analysis female sex (HR=0.61, p=.02), chemotherapy (HR=0.66, p=.05), node negative (HR=0.47, p=.005) and TFPI CC polymorphism (HR=0.35, p=.01) were independently associated with improved DFS. The prevalence of FVL (0.7%) and PT (2.2%) polymorphisms was too low to detect any interaction with TFPI polymorphism and DFS. Conclusions: These findings indicate that the inherited anticoagulant homozygous -33T-->C TFPI polymorphism may protect against colon cancer recurrence, and suggest a causal role for the coagulation system in cancer outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".