Seasonal variations of date of diagnosis and birth for neuroblastoma patients in Italy

Analysis of seasonal variation of diagnosis or birth of childhood cancers may provide useful insight about possible aetiological risk factors, such as infectious agents and environmental exposures, but studies on neuroblastoma are lacking. Two thousand seven hundred fifty-six cases of neuroblastoma, diagnosed between 1980 and 2010, registered in the Italian Neuroblastoma Registry, were included in the study. Subgroup analyses were carried out by age, gender and stage at diagnosis. Seasonal trend was assessed by a harmonic function in a Poisson regression model, adjusted for the number of live births. No trend in the date of diagnosis was found either in the entire cohort or in the various sub-groups. Similarly, a seasonal trend of birth was not observed in the whole cohort. Conversely, in the subgroup of infants with stage 4S, a significant peak of July births was found (23.6% increment from the average, p = 0.042). The summer peak was confirmed after stratifying 4S patients by gender and period of diagnosis. A major effect of risk factors related to seasonality does not appear to affect the risk of developing neuroblastoma. However, the time pattern of birth observed by stage at diagnosis is consistent with the hypothesis that Stage 4S is a distinct disease with probably a different aetiology, as indicated by investigations on its metastatic pattern and its peculiar gene expression. An aetiological role of seasonally related factors, e.g., favouring the survival of defective neural crest stem cells, remains speculative and need confirmation by independent studies.