Evidence of seasonal variation of childhood acute lymphoblastic leukemia in Sweden
Preprint, 2023
Background B-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.
Methods We 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.
Results An 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.
Conclusions Diagnosis 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.
Methods We 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.
Results An 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.
Conclusions Diagnosis 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.
Author
Gleb Bychkov
Karolinska Institutet
Benedicte Bang
Karolinska Institutet
Niklas Engsner
Karolinska Institutet
Mats Marshall Heyman
Karolinska Institutet
Anna Skarin Nordenvall
Karolinska University Hospital
Karolinska Institutet
Giorgio Tettamanti
Karolinska Institutet
Karolinska University Hospital
Nikolas Herold
Karolinska University Hospital
Fulya Taylan
Karolinska Institutet
Emeli Ponten
Karolinska Institutet
Jan Albert
Karolinska University Hospital
Karolinska Institutet
Rebecka Jörnsten
University of Gothenburg
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Claes Strannegård
University of Gothenburg
Chalmers, Computer Science and Engineering (Chalmers), Data Science and AI
Ann Nordgren
Karolinska Institutet
University of Gothenburg
Sahlgrenska University Hospital
Karolinska University Hospital
Subject Categories (SSIF 2025)
Cancer and Oncology
DOI
10.1101/2023.02.12.23285595