| Title: | Polygenic risk score to define risk of cancer-associated thrombosis among patients with lung cancer in a population-based study |
| Journal: | Lung Cancer |
| Published: | 25 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40882293/ |
| DOI: | https://doi.org/10.1016/j.lungcan.2025.108712 |
Publication 19668
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: 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.</p>
METHODS: 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).</p>
RESULTS: 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.</p>
CONCLUSION: The PGS identified lung cancer patients at higher inherited risk for VTE, suggesting its potential for personalized prophylaxis and improved clinical outcomes.</p>
18 Keywords
- Aged
- Factor V
- Female
- Genetic Predisposition to Disease
- Genetic Risk Score
- Humans
- Incidence
- Lung Neoplasms
- Male
- Middle Aged
- Multifactorial Inheritance
- Mutation
- Prothrombin
- Risk Assessment
- Risk Factors
- Thrombosis
- United Kingdom
- Venous Thromboembolism
10 Authors
- Alfonso Tafur
- Adeeb Sebai
- Zhuqing Shi
- Jun Wei
- Huy Tran
- S Lilly Zheng
- Seth Krantz
- Thomas Hensing
- Aaron S Mansfield
- Jianfeng Xu
Enabling scientific discoveries that improve human health