- Olga V. Gran1,*,
- Erin N. Smith2,
- Sigrid K. Braekkan1,
- Hilde Jensvoll1,
- Terry Solomon2,
- Kristian Hindberg1,
- Tom Wilsgaard1,
- Frits R. Rosendaal3,
- Kelly A. Frazer2 and
- John-Bjarne Hansen1
- 1 UiT, The Arctic University of Norway;
- 2 University of California, San Diego;
- 3 Leiden University Medical Center, C7-P
- ↵* Corresponding author; email:
Venous thromboembolism occurs frequently in cancer patients. Two variants in the Factor 5 (F5) gene (rs6025 encodes the Leiden mutation (FVL) R506Q, and rs4524 encodes K858R) have been found to be associated with venous thromboembolism. We assessed the joint effect of active cancer and these two F5 variants, respectively, on venous thromboembolism risk in a case-cohort study. Cases with a first venous thromboembolism (n=609) and a randomly selected age-weighted sub-cohort (n=1961) were sampled from the general population in Tromso, Norway. A venous thromboembolism was classified as cancer-related if it occurred in the period six months before to two years after a cancer diagnosis. Active cancer was associated with an 8.9-fold higher risk of venous thromboembolism (95% CI 7.2-10.9). The risk of a cancer-related venous thromboembolism was 16.7-fold (95% CI 9.9-28.0) higher in subjects heterozygous for rs6025 compared with non-carriers of the FVL allele without active cancer. In subjects with active cancer the risk of venous thromboembolism was 15.9-fold higher (95% CI 9.1-27.9) in those with one risk allele at rs4524, and 21.1-fold (95% CI 12.4-35.8) higher in those with two risk alleles compared with non-carriers without active cancer. A synergistic interaction was observed between active cancer and FVL (relative excess risk due to interaction 7.0; 95% CI 0.5-14.4) and rs4524 (relative excess risk due to interaction 15.0; 95% CI 7.5 -29.2). The incidence of venous thromboembolism during the initial six months following a cancer diagnosis was particularly steep in subjects with risk alleles at these loci. This implies that the combination of cancer and F5 variants yields a synergistic increase on venous thromboembolism risk.
- Received April 5, 2016.
- Accepted June 10, 2016.
- Copyright © 2016, Ferrata Storti Foundation