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Additional file 3: Additional Table 1. Association between the incidence rate of childhood acute lymphoblastic leukaemia and three potential ecological confounders characterising the municipality of residence at birth: size of urban unit, residential UV radiation exposure, and a socioeconomic deprivation index (RNCE, 1990–2015).

Additional file 4: Additional Table 2. Distribution of the at-risk population a over 1990-2015 by category of crop density and potential confounding factor stratum (size of urban unit, residential UV radiation exposure, and a French deprivation index), children born in 1990-2015, mainland France.

Additional file 5: Additional Table 3. Association between AL incidence rate and crop densitya in municipalities of residence at birth with restriction to municipalities situated outside of the Paris urban unit, and municipalities in urban units with a population of less than 100,000, mainland France, RNCE, 1990–2015.

Additional file 6: Additional Table 4. Association between ALL and BCP-ALL incidence rates and crop densitiesa in the municipalities of residence at birth, stratified by age group (mainland France, RNCE, 1990–2015).

Additional file 7: Additional Table 5. Bibliography.

Additional file 1: Additional Figure 1. Annual standardized incidence ratio (SIR) of childhood AL, RNCE, 1990-2015, mainland France.

Background Significant increases in childhood cancer incidence since the 1970s have been consistently reported worldwide, but the persistence of the increase on recent periods is discussed. No conclusion can be drawn concerning the spatial variations of childhood cancer, either. This study is an in‐depth investigation of the spatial and temporal variations of childhood cancer in France. An extensive review of all the studies published since 2000 on those issues is provided. Methods The study included 25 877 cases of childhood cancer registered nationwide over 2000‐2014. The spatial heterogeneity (overdispersion, autocorrelation, overall heterogeneity) was tested, on two geographic scales, and two spatial scan methods were used to detect clusters of cases. The annual average percent change (AAPC) in incidence rate was estimated with Poisson regression models, and joinpoint analyses were considered. Results Glioma and non‐Hodgkin lymphoma cases exhibited some spatial heterogeneity and two large clusters were detected. Overall, the incidence rate of childhood cancer was stable over 2000‐2014 (AAPC = −0.1% [−0.3%; 0.2%]). A log‐linear positive trend was significantly evidenced for gliomas other than pilocytic astrocytomas (AAPC = 1.8% [0.9%; 2.7%]), with some suggestion of a leveling‐off at the end of the period, while Burkitt lymphoma and germ cell tumor incidence rates decreased (AAPC = −2.2% [−3.8%; −0.5%] and AAPC = −1.9% [−3.4%; −0.3%], respectively). No spatial heterogeneity or significant time variation was evidenced for other cancers. Conclusion Several types of childhood cancer displayed some spatial heterogeneity and two large clusters were detected, the origins of which are to be investigated and might include differences in case ascertainment. Overall, the results do not support a sustained increase in incidence rates of childhood cancer in recent years.