# Genetic markers of thrombophilia as predictors of outcome in colorectal cancer

## TL;DR

This study explores how genetic markers related to blood clotting may predict outcomes in colorectal cancer patients, with some markers showing different effects based on sex.

## Contribution

The study identifies specific genetic variants associated with cancer recurrence and mortality in colorectal cancer patients, with sex-specific effects.

## Key findings

- The CNTN6 rs6764623, PTGS2 rs20417, and RGS7 rs2502448 variants are linked to cancer recurrence risk.
- The ITGB3 rs5918 variant predicts all-cause mortality, especially in male patients.
- Sex-specific impacts of SNPs suggest the need for further research in larger and more balanced patient cohorts.

## Abstract

Colorectal cancer (CRC) is the second leading cause of malignancy-related death worldwide, representing a significant health concern. Understanding the disease pathogenesis and identifying potential prognostic biomarkers is critical for improving patients’ clinical outcomes. Haemostatic components implicated in cancer-associated thrombosis (CAT) seem to favour CRC progression. As such, genetic markers of thrombophilia might be potential prognostic biomarkers among patients with this malignant disease. To offer perspectives, a retrospective cohort study with 204 CRC patients was conducted to investigate the impact of seven germline haemostatic gene determinants on patient prognosis. A sex-stratified analysis was performed as the variants seem to have a distinct influence depending on the patient’s sex. Genomic DNA was extracted from FFPE samples enriched in tumour cells. While the polymorphisms CNTN6 rs6764623 (CC/CA vs. AA; adjusted hazard ratio (aHR) = 0.44; 95% confidence interval (CI), 0.20–0.96; P = 0.040), PTGS2 rs20417 (GG vs. CC/CG; aHR = 2.88; 95%CI, 1.10–7.51; P = 0.031) and RGS7 rs2502448 (TT vs. CT/CC; aHR = 2.35; 95%CI, 1.20–4.61; P = 0.013) were associated with the five-year risk of cancer recurrence, ITGB3 rs5918 was a predictor of the risk of death due to all causes, particularly among male patients (TT vs. CT/CC; aHR = 2.05; 95% confidence interval (CI), 1.13–3.72; P = 0.019). While a sex-specific impact of the SNPs was observed, further investigation in larger cohorts, particularly with an increased representation of female patients, is required to confirm these associations. Collectively, these markers could help improve the prognosis assessment of CRC patients towards a more personalised intervention.

The online version contains supplementary material available at 10.1007/s11239-025-03106-1.