TY - JOUR
T1 - Polygenic risk scores for prediction of cancer-associated venous thromboembolism in the UK Biobank cohort study
AU - Guman, Noori A. M.
AU - Mulder, Frits I.
AU - Ferwerda, Bart
AU - Zwinderman, Aeilko H.
AU - Kamphuisen, Pieter W.
AU - Büller, Harry R.
AU - van Es, Nick
N1 - Funding Information: This study was conducted using the UK Biobank Resource under Application Number 56145. F.I.M. N.v.E. and N.A.M.G. were responsible for the conception and design of the study. F.I.M. applied for the use of the data and downloaded the data from the UK Biobank showcase. N.A.M.G. F.I.M. and B.F. performed the statistical analysis. N.A.M.G. drafted the first version of the manuscript. All authors revised the manuscript for intellectual content, approved the final version of the manuscript, take full responsibility for the content, and agreed to its submission. 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. Funding Information: Funding information This study was supported by an unrestricted research grant from the Tergooi Academy, Hilversum, The Netherlands. The funding source had no role in the design of the study, writing, or decisions on publication. The authors received no compensation from any company or agency to write this article. Publisher Copyright: © 2023 The Authors
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - genetic testing
KW - neoplasms
KW - risk assessment
KW - thrombosis
KW - venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85170281458&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jtha.2023.07.009
DO - https://doi.org/10.1016/j.jtha.2023.07.009
M3 - Article
C2 - 37481074
SN - 1538-7933
VL - 21
SP - 3175
EP - 3183
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 11
ER -