Fibrinogen gamma gene rs2066865 and risk of cancer-related venous thromboembolism
Benedikte Paulsen,
Hanne Skille,
Erin N. Smith,
Kristian Hveem,
Maiken E. Gabrielsen,
Sigrid K. Brækkan,
Frits R. Rosendaal,
Kelly A. Frazer,
Olga V. Gran,
John-Bjarne Hansen
Affiliations
Benedikte Paulsen
K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway
Hanne Skille
K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway
Erin N. Smith
Department of Pediatrics and Rady’s Children’s Hospital, University of California, San Diego, La Jolla, CA, USA
Kristian Hveem
St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway;HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway;K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway
Maiken E. Gabrielsen
HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway;K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway
Sigrid K. Brækkan
K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway;Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Frits R. Rosendaal
K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway;Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Kelly A. Frazer
K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway;Department of Pediatrics and Rady’s Children’s Hospital, University of California, San Diego, La Jolla, CA, USA
Olga V. Gran
K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway
John-Bjarne Hansen
K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway;Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Venous thromboembolism (VTE) is a frequent complication in patients with cancer. Homozygous carriers of the fibrinogen gamma gene (FGG) rs2066865 have a moderately increased risk of VTE, but the effect of the FGG variant in cancer is unknown. We aimed to investigate the effect of the FGG variant and active cancer on the risk of VTE. Cases with incident VTE (n=640) and a randomly selected age-weighted sub-cohort (n=3,734) were derived from a population-based cohort (the Tromsø study). Cox-regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for VTE according to categories of cancer and FGG. In those without cancer, homozygosity at the FGG variant was associated with a 70% (HR 1.7, 95% CI: 1.2–2.3) increased risk of VTE compared to non-carriers. Cancer patients homozygous for the FGG variant had a two-fold (HR 2.0, 95% CI: 1.1–3.6) higher risk of VTE than cancer patients without the variant. Moreover, the six-months cumulative incidence of VTE among cancer patients was 6.4% (95% CI: 3.5–11.6) in homozygous carriers of FGG and 3.1% (95% CI: 2.3–4.7) in those without risk alleles. A synergistic effect was observed between rs2066865 and active cancer on the risk of VTE (synergy index: 1.81, 95% CI: 1.02–3.21, attributable proportion: 0.43, 95% CI: 0.11–0.74). In conclusion, homozygosity at the FGG variant and active cancer yielded a synergistic effect on the risk of VTE.
