Clustering of childhood acute leukemia in Finland: a nationwide register-based study.
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PURPOSE: Acute leukemia is the most common childhood malignancy, with suspected contributions from environmental factors and immune responses to common pathogens. A recent meta-analysis indicated possible spatiotemporal clustering, though the findings were hindered by data quality limitations. We investigated spatial and spatiotemporal clustering of childhood leukemia using advanced methods and complete residential histories. METHODS: We included patients aged 0-17 years diagnosed in 1990-2019, using data from the Finnish Cancer Registry. A 1:3 age- and sex-matched case-control design was employed and residential history data with exact coordinates was collected. Clustering was evaluated using the Cuzick-Edwards test, Knox test, Kulldorff's scan statistic, and Jacquez's Q statistic. RESULTS: The dataset included 1,626 childhood leukemia cases (median age 5.0 years, 54% male). The Knox test revealed no evidence of spatiotemporal clustering. However, the Cuzick-Edwards test revealed spatial clustering at diagnosis addresses for children under 1 year (OR 1.35, 95% CI 1.14-1.57). Further analysis with Jacquez's Q test using complete residential histories identified significant spatiotemporal clustering in young children (ages 1.5-5.99 years) with acute lymphoblastic leukemia (ALL, p = 0.037). We also tested for co-incidence between leukemia and type 1 diabetes but found no clustering. CONCLUSION: Overall, we found limited evidence for clustering. In the subgroup analyses, significant spatiotemporal clustering in acute lymphoblastic leukemia cases among children aged 1.5-5.99 years was observed, coinciding with the peak incidence in early childhood. Previous research has shown that this age group has distinct genetic characteristics and may possess a unique etiology.