Combined effects of five prothrombotic genotypes and cancer on the risk of a first venous thromboembolic event

• Published in: Journal of Thrombosis and Haemostasis
• Main Authors: Skille, Hanne, Paulsen, Benedikte, Hveem, Kristian, Gabrielsen, Maiken Elvestad, Brumpton, Ben Michael, Hindberg, Kristian, Gran, Olga Vikhammer, Rosendaal, Frits Richard, Brækkan, Sigrid Kufaas, Hansen, John-Bjarne
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley Online Library 2020
• Subjects: Tromsø
• Online Access: https://hdl.handle.net/11250/2726867; https://doi.org/10.1111/jth.15011

Background: The role of combined prothrombotic genotypes in cancer-related venous thromboembolism (VTE) is scarcely studied. We aimed to investigate the impact of a 5-single nucleotide polymorphism (SNP) score on the risk of VTE in patients with and without cancer using a population-based case-cohort. Methods: Cases with a first VTE (n = 1493) and a subcohort (n = 13 072) were derived from the Tromsø Study (1994-2012) and the Nord-Trøndelag Health Study (1995-2008). Five SNPs previously reported as a risk score were genotyped: ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865), and F11 (rs2036914). Hazard ratios (HRs) for VTE were estimated according to cancer status and the number of risk alleles in the 5-SNP score (0-1, 2-3, and ≥4 alleles). Results: During a median follow-up of 12.3 years, 1496 individuals were diagnosed with cancer, of whom 232 experienced VTE. The VTE risk increased with the number of risk alleles in the 5-SNP score among subjects without and with cancer. In cancerfree subjects, the HR was 2.17 (95% confidence interval [CI] 1.79-2.62) for ≥4 versus 0-1 risk alleles. In cancer patients, the corresponding HR was 1.93 (95% CI 1.28-2.91). The combination of cancer and ≥4 risk alleles yielded a 17-fold (HR 17.1, 95% CI 12.5- 23.4) higher risk of VTE compared with cancer-free subjects with 0-1 risk alleles. Conclusion: The risk of VTE increases with the number of prothrombotic risk alleles in subjects with and without cancer, and the combination of prothrombotic risk alleles and cancer leads to a highly elevated risk of VTE publishedVersion This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis