Hanne Skille1, Benedikte Paulsen1, Kristian Hveem2,3, Maiken E Gabrielsen2,3, Ben Brumpton2,3, Kristian Hindberg1, Olga V Gran1, Frits R Rosendaal1,4, Sigrid K Braekkan1,5, John-Bjarne Hansen1,5. 1. K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway. 2. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway. 3. HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway. 4. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. 5. Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
Abstract
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 cancer-free 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.
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 cancer-free subjects, the HR was 2.17 (95% confidence interval [CI] 1.79-2.62) for ≥4 versus 0-1 risk alleles. In cancerpatients, 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.
Authors: Alok A Khorana; Nigel Mackman; Anna Falanga; Ingrid Pabinger; Simon Noble; Walter Ageno; Florian Moik; Agnes Y Y Lee Journal: Nat Rev Dis Primers Date: 2022-02-17 Impact factor: 65.038
Authors: Noori A M Guman; Roos J van Geffen; Frits I Mulder; Thijs F van Haaps; Vahram Hovsepjan; Mariette Labots; Geert A Cirkel; Filip Y F L de Vos; Albert J Ten Tije; Laurens V Beerepoot; Vivianne C G Tjan-Heijnen; Hanneke W M van Laarhoven; Paul Hamberg; Annelie J E Vulink; Maartje Los; Aeilko H Zwinderman; Bart Ferwerda; Martijn P J K Lolkema; Neeltje Steeghs; Harry R Büller; Pieter W Kamphuisen; Nick van Es Journal: J Thromb Haemost Date: 2021-09-06 Impact factor: 16.036