Polygenic risk scores for prediction of cancer-associated venous thromboembolism in the UK Biobank cohort study.
genetic testing
neoplasms
risk assessment
thrombosis
venous thromboembolism
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
06
04
2023
revised:
06
07
2023
accepted:
09
07
2023
medline:
23
10
2023
pubmed:
23
7
2023
entrez:
22
7
2023
Statut:
ppublish
Résumé
Guidelines recommend thromboprophylaxis for patients with cancer at high risk of venous thromboembolism (VTE). Polygenic risk scores may improve VTE prediction but have not yet been evaluated in patients with cancer. We assessed the performance of the 5-, 37-, 297-, extended 297- (additionally including factor V Leiden and prothrombin G20210A), and 100-single-nucleotide polymorphism (SNP) scores in predicting cancer-associated VTE in the UK Biobank, a population-based, prospective cohort study. The primary outcome was VTE during 12 months after cancer diagnosis. Cancer and VTE diagnosis were based on ICD-10 codes. Discrimination was evaluated by c-indices and subdistribution hazard ratios in the upper vs 3 lower quartiles of the scores in a competing risk model. As a comparison, the c-index was calculated for the Khorana cancer type risk classification. Of 36 150 patients with cancer (median age, 66 years; 48.7% females), 1018 (2.8%) developed VTE. C-indices at 12 months ranged from 0.56 (95% CI, 0.54-0.58) for the 5-SNP to 0.60 (95% CI, 0.58-0.62) for the extended 297-SNP scores. The subdistribution hazard ratios ranged from 1.36 (95% CI, 1.19-1.56) for the 5-SNP to 1.90 (95% CI, 1.68-2.16) for the extended 297-SNP scores and were consistent after adjusting for cancer type. For the Khorana cancer type classification, the c-index was 0.60 (95% CI, 0.58-0.61), which increased to 0.65 (95% CI, 0.63-0.67, +0.05; 95% CI, 0.04-0.07) when combined with the extended 297-SNP score. These findings demonstrate that polygenic VTE risk scores can identify patients with cancer with a 1.9-fold higher VTE risk independent of cancer type. Combined clinical-genetic scores to improve cancer-associated VTE prediction should be evaluated further.
Sections du résumé
BACKGROUND
Guidelines recommend thromboprophylaxis for patients with cancer at high risk of venous thromboembolism (VTE). Polygenic risk scores may improve VTE prediction but have not yet been evaluated in patients with cancer.
OBJECTIVES
We assessed the performance of the 5-, 37-, 297-, extended 297- (additionally including factor V Leiden and prothrombin G20210A), and 100-single-nucleotide polymorphism (SNP) scores in predicting cancer-associated VTE in the UK Biobank, a population-based, prospective cohort study.
METHODS
The primary outcome was VTE during 12 months after cancer diagnosis. Cancer and VTE diagnosis were based on ICD-10 codes. Discrimination was evaluated by c-indices and subdistribution hazard ratios in the upper vs 3 lower quartiles of the scores in a competing risk model. As a comparison, the c-index was calculated for the Khorana cancer type risk classification.
RESULTS
Of 36 150 patients with cancer (median age, 66 years; 48.7% females), 1018 (2.8%) developed VTE. C-indices at 12 months ranged from 0.56 (95% CI, 0.54-0.58) for the 5-SNP to 0.60 (95% CI, 0.58-0.62) for the extended 297-SNP scores. The subdistribution hazard ratios ranged from 1.36 (95% CI, 1.19-1.56) for the 5-SNP to 1.90 (95% CI, 1.68-2.16) for the extended 297-SNP scores and were consistent after adjusting for cancer type. For the Khorana cancer type classification, the c-index was 0.60 (95% CI, 0.58-0.61), which increased to 0.65 (95% CI, 0.63-0.67, +0.05; 95% CI, 0.04-0.07) when combined with the extended 297-SNP score.
CONCLUSION
These findings demonstrate that polygenic VTE risk scores can identify patients with cancer with a 1.9-fold higher VTE risk independent of cancer type. Combined clinical-genetic scores to improve cancer-associated VTE prediction should be evaluated further.
Identifiants
pubmed: 37481074
pii: S1538-7836(23)00571-8
doi: 10.1016/j.jtha.2023.07.009
pii:
doi:
Substances chimiques
Anticoagulants
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3175-3183Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interests N.A.M.G., F.I.M., A.H.Z., and B.F. have no conflicts of interest to declare. H.R.B. reports personal fees from Daiichi-Sankyo, Bayer Healthcare, BMS/Pfizer, Boehringer Ingelheim, Portola, Medscape, Eli Lilly, Sanofi Aventis, and Ionis. P.W.K. has received research grants from Daiichi Sankyo, Roche Diagnostics, and the Tergooi Academy. N.v.E. reports advisory board honoraria from Daiichi-Sankyo, Bayer, and LEO Pharma, which were transferred to his institute.