Background: Infections account for about 15% of human cancers globally. Although abnormal hematologic profiles and bone marrow suppression are common in patients with dengue, whether dengue is associated with a higher risk of leukemia has not been investigated. Methods: We conducted a nationwide population-based cohort study by analyzing the National Health Insurance Research Databases in Taiwan. Laboratory-confirmed dengue patients between 2002 and 2011 were identified; five matched non-dengue controls were randomly selected for each patient. Follow-up ended on December 31, 2015. Multivariate Cox proportional hazard regression models were used to evaluate the effect of dengue virus infection on the risk of leukemia. Cancers other than leukemia were used as falsification endpoints to evaluate the validity of this study. Results: We identified 12,573 patients with dengue and 62,865 non-dengue controls. Patients with dengue had a higher risk of leukemia [adjusted HR, 2.03; 95% confidence interval (CI), 1.16-3.53]. Stratified analyses by different follow-up periods showed that dengue virus infection was significantly associated with a higher risk of leukemia only between 3 and 6 years after infection (adjusted HR, 3.22; 95% CI, 1.25-8.32). There was no significant association between dengue and the risk of other cancers. Conclusions: This study provides the first epidemiologic evidence for the association between dengue virus infection and leukemia. Impact: Considering the rapidly increasing global incidence of dengue and the burden of leukemia, further studies are required to verify this association and to unravel the potential mechanisms of pathogenesis.
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