Space-time clustering of childhood cancers in Switzerland: A nationwide study

The aetiology of childhood cancers remains largely unknown. It has been hypothesized that infections may be involved and that mini-epidemics thereof could result in space-time clustering of incident cases. Most previous studies support spatio-temporal clustering for leukaemia, while results for other diagnostic groups remain mixed. Few studies have corrected for uneven regional population shifts which can lead to spurious detection of clustering. We examined whether there is space-time clustering of childhood cancers in Switzerland identifying cases diagnosed at age <16 years between 1985 and 2010 from the Swiss Childhood Cancer Registry. Knox tests were performed on geocoded residence at birth and diagnosis separately for leukaemia, acute lymphoid leukaemia (ALL), lymphomas, tumours of the central nervous system, neuroblastomas and soft tissue sarcomas. We used Baker's Max statistic to correct for multiple testing and randomly sampled time-, sex- and age-matched controls from the resident population to correct for uneven regional population shifts. We observed space-time clustering of childhood leukaemia at birth (Baker's Max p=0.045) but not at diagnosis (p=0.98). Clustering was strongest for a spatial lag of <1 km and a temporal lag of <2 years (Observed/expected close pairs: 124/98; p Knox test=0.003). A similar clustering pattern was observed for ALL though overall evidence was weaker (Baker's Max p=0.13). Little evidence of clustering was found for other diagnostic groups (p>0.2). Our study suggests that childhood leukaemia tends to cluster in space-time due to an etiologic factor present in early life. What's new? Childhood leukaemia tends to occur in space-time clusters, suggesting an infectious etiology. In this analysis of data from the Swiss Childhood Cancer Registry, space-time clustering of childhood leukaemia was observed specifically around the time of birth but not at diagnosis. Clustering was not detected for other childhood cancers. The study is unique in that it corrects for uneven shifts in regional population, a potential source of bias in earlier studies, at high geographic resolution. The small spatial (<1 km) and temporal (<2 years) scale of the clustering could indicate a leukemogenic infection occurring around birth or in utero.