Polygenic risk score to define risk of cancer-associated thrombosis among patients with lung cancer in a...

Venous thromboembolism (VTE) is a major complication in lung cancer, and remains challenging to predict with current risk models. This study assesses the utility of a Polygenic Score (PGS) for VTE risk stratification in lung cancer patients.

Analyzing UK Biobank data with 3,241 lung cancer patients, we explored the association between a high PGS, with and without positive monogenic mutations (factor V Leiden [FVL]/ prothrombin gene mutation [PGM]), and VTE incidence. Two definitions of VTE incidence were used: "restricted location VTE" (pulmonary embolism or lower extremity thrombosis) and "any VTE" (inclusive of all venous thromboses).

A high PGS was strongly associated with an increased VTE, including in subgroup analysis with adjustment for comorbidities. A previous VTE (Hazard ratio [HR]: 5.5) and metastasis (HR: 2.52) predicted increased risk of VTE. In addition, the top PGS quartile predicted VTE in both the any VTE definition: HR 1.35 (with FVL/PGM) and 1.39 (without FVL/PGM); and in the restricted location VTE: HR 1.38 (without FVL/PGM); all p ≤ 0.05. The 12-month VTE incidence confirmed the predictive discrimination of the PGS regardless of FVL/PGM status.

The PGS identified lung cancer patients at higher inherited risk for VTE, suggesting its potential for personalized prophylaxis and improved clinical outcomes.