Evidence of seasonal variation of childhood acute lymphoblastic leukemia in Sweden

BackgroundB-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in children and adolescents. A combination of genetic predisposition, exposures to diverse microbiota, infections, and an immature immune system have been associated with BCP-ALL development. Genetic aberrations causing the progression of preleukemic cells to overt BCP-ALL have been identified, but drivers behind these aberrations remain largely unknown. MethodsWe analyzed seasonal variation in 1,380 BCP-ALLs, 385 acute myeloid leukemias (AML), 3,052 solid tumors and 1,945 brain tumors retrieved from the population-based Swedish Childhood Cancer Registry (SCCR), aged 0-18 years at diagnosis and diagnosed between 1995-2017. Cases were first aggregated into three types of quarters (3-month periods) based on the time of BCP-ALL diagnosis. Then, data was analyzed using a Bayesian Generalized Auto Regressive Integrated Moving Average with external variables (GARIMAX) model, adapted for count data via a negative binomial distribution. ResultsAn informative seasonal variation in BCP-ALL with peak quarters in Jul-Sep and Jun-Aug was identified. Manual inspection revealed that the largest number of BCP-ALL cases (138 (10%)) was observed in August. No seasonal variation was detected in the comparison groups of childhood AML, brain tumors, or solid tumors. ConclusionsDiagnosis of childhood BCP-ALL in Sweden displays seasonal variation with a peak during the summer months, in contrast to other tumor types. We present putative explanation models for this incidence peak that build on the hypothesis of infectious exposure/-s triggering the final progression to BCP-ALL diagnosis in at-risk individuals. Further studies using GARIMAX in larger populations with genetically confirmed BCP-ALL subtypes are warranted.