Background: Guidelines recommend primary thromboprophylaxis for selected cancer patients at high risk of venous thromboembolism (VTE). Improvement of traditional clinical risk assessment models for VTE in cancer patients is needed.

Aims: To assess the predictive performance of three polygenic VTE risk scores derived in the general population (De Haan et al. 2012 [5-SNP score], Klarin et al. 2019 [297-SNP score], and Lindström et al. 2019 [37-SNP score]) in cancer patients enrolled in the UK Biobank, a large-scale prospective, observational cohort.

Methods: Participants with an incident cancer diagnosis after UK Biobank enrollment were included, using data from cancer registries or inpatient diagnosis data. Those with an anticoagulant therapy prescription at enrollment or history of VTE were excluded. The primary outcome was pulmonary embolism or deep-vein thrombosis. Patients were followed for 12 months after cancer diagnosis. Performance of the continuous scores was assessed by time-dependent c-indices and subdistribution hazard ratios (SHR) in univariable and multivariable analyses adjusted for sex and age. The risk in patients in the upper quartile of the polygenic scores was compared to that in the lower three quartiles.

Results: 36,479 cancer patients (median age 66; 49% females) were included of whom 874 (2.4%) developed VTE during 12-month follow-up. All continuous scores were significantly associated with VTE in univariable and multivariable analyses (SHRs 1.3 to 1.5). The 297-SNP score showed the best discrimination (c-index 0.59, 95%-CI: 0.58-0.61). For this score, the cumulative VTE incidence was 3.6% (95%CI: 3.2-4.0) in the upper quartile versus 2.0% (95%CI: 1.8-2.2) in the lower quartiles (SHR 1.8, 95%CI: 1.6-2.1). Performance of all scores is summarized in the Table and Figure.

Conclusion(s): Polygenic VTE risk scores developed for the general population can identify cancer patients with about a 2-fold increased VTE risk, and may potentially improve VTE risk assessment on top of clinical risk scores.

Table

Association between polygenic risk scores and cancer-associated venous thromboembolism

Figure

Performance of polygenic VTE risk scores during 12 months after incident cancer diagnosis. Time-to-event curves with death as competing risk during 12 months after incident cancer diagnosis in 25% of patients with the highest scores and 75% with lower scores -A-C-. Receiver operatoring curve -ROC- of the continuous polygenic risk scores at 12 months after incident cancer diagnosis -D-.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/polygenic-risk-scores-for-prediction-of-cancer-associated-venous-thromboembolism-a-uk-biobank-analysis/