Cancer risk in long-term users of vitamin K antagonists: A population-based case–control study

Authors

  • Anton Pottegård,

    Corresponding author
    1. Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense C, Denmark
    • Pharmacist, Clinical Pharmacology, University of Southern Denmark, JB Winsløwsvej 19, 2, 5000 Odense C, Denmark
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    • Tel.: 0045-2891-3340

  • Søren Friis,

    1. Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen Ø, Denmark
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  • Jesper Hallas

    1. Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense C, Denmark
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    • Conflicts of interest: J.H. has participated in research projects funded by and received fees for consulting from Nycomed, the manufacturer of warfarin. A.P. and S.F. declare no conflicts of interest.


Abstract

Some evidence suggests that long-term use of vitamin K antagonists (VKAs) has a cancer chemopreventive effect. Such an effect would have considerable implications in terms of understanding tumor biology. To evaluate if long-term VKA treatment influences the risk of developing cancer, we performed a matched case–control analysis. We used data from four Danish nationwide registers. Cases were all Danish individuals with a first-time cancer diagnosis (except nonmelanoma skin cancer) between 2000 and 2009. For each case, eight controls, matched by birth year and gender, were selected from the source population by risk-set sampling. Long-term VKA use was defined as exposure to VKA for a period of 3 or more years. Conditional logistic regression was used to compute odds ratios (ORs) for cancer associated with long-term VKA exposure, adjusting for potential confounders. Prespecified subanalyses were performed for selected cancer sites, subgroups and measures of exposure. A total of 238,196 cases and 1,713,176 controls were included. The adjusted OR for cancer associated with long-term VKA exposure was 0.99 (95% CI: 0.95–1.02). Long-term VKA use was associated with increased ORs for alcohol- or obesity-related cancer sites, whereas we observed a decreased risk of prostate cancer (OR: 0.86; 95% CI: 0.78–0.95). Our study does not support a general chemopreventive effect of VKA drugs. However, in accordance with findings from previous studies, we found an inverse association between use of VKA and prostate cancer.

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