Impact of Inherited Thrombophilia on Cancer-Associated Thrombosis: A Systematic Review and Meta-Analysis

Background:Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality in patients with malignancy. The contribution of inherited thrombophilia remains incompletely defined. Objectives: To evaluate the association between inherited thrombophilia and other genetic determinants and CAT risk in adults with malignancy. Methods: We conducted a PRISMA 2020-compliant systematic review and meta-analysis of observational studies comparing genetic determinants in patients with cancer with and without VTE. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using Mantel–Haenszel models. Risk of bias and certainty of evidence were assessed using the Newcastle–Ottawa Scale and GRADE, respectively. Results: Twenty-one studies including 4,479 patients (1,115 with VTE) were included. Factor V Leiden (FVL) was associated with increased odds of CAT (OR 2.48, 95% CI 1.75–3.51; I²=32%), with consistent findings after exclusion of device- or catheter-related thrombosis. Heterozygous FVL was associated with CAT (OR 1.86, 95% CI 1.27–2.73), whereas the homozygous estimate was imprecise (OR 3.42, 95% CI 0.75–15.59). Prothrombin G20210A was associated with CAT (OR 2.67, 95% CI 1.56–4.58; I²=0%). Exploratory analyses yielded estimates for MTHFR (OR 1.40, 95% CI 1.02–1.93) and blood group O (OR 0.40, 95% CI 0.23–0.70); the latter was based on only two studies. Evidence for rarer determinants was sparse. Certainty was moderate for FVL and low or very low for other determinants. Conclusions: FVL and prothrombin G20210A are associated with increased odds of CAT. Current evidence does not support universal genetic screening but warrants prospective evaluation of the incremental predictive value of genetic markers beyond established CAT risk models.