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Space-time clustering patterns in childhood leukaemia support a role for infection
J M Birch1, F E Alexander, V Blair
1CRC Paediatric & Familial Cancer Research Group, Royal Manchester Children's Hospital, Stancliffe, UK.
Abstract:
Previous studies of space-time clustering in childhood leukaemia have produced equivocal and inconsistent results. To address this issue we have used Manchester Children's Tumour Registry leukaemia data in space-time clustering analyses. Knox tests for space-time interactions between cases were applied with fixed thresholds of close in space, <5 km and close in time <1 year apart. Addresses at birth as well as diagnosis were utilized. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. All methods showed highly significant evidence of space-time clustering based on place of birth and time of diagnosis, particularly for all leukaemias aged 0-14 and 0-4 years, and acute lymphoblastic leukaemia (ALL) 0-4 years. Some results based on location at diagnosis were significant but mainly gave larger P-values. The results are consistent with an infectious hypothesis. Furthermore, we found an excess of male cases over females involved in space-time pairs. We suggest this may be related to genetic differences in susceptibility to infection between males and females. These findings provide the basis for future studies to identify possible infectious agents.
Insights
Childhood leukaemia cases show significant space-time clustering, particularly when considering birth location and diagnosis time. These findings suggest an infectious cause for childhood leukaemia.
Area of Science:
- Epidemiology
- Paediatric Oncology
- Spatial Statistics
Background:
- Previous studies on space-time clustering in childhood leukaemia have yielded inconsistent results.
- Understanding geographical and temporal patterns is crucial for identifying potential causes of childhood cancers.
Purpose of the Study:
- To investigate space-time clustering of childhood leukaemia using robust statistical methods.
- To identify specific age groups and leukaemia subtypes exhibiting significant clustering.
- To explore potential aetiological factors, such as infectious agents.
Main Methods:
- Utilized Manchester Children's Tumour Registry data for childhood leukaemia cases.
- Applied Knox tests for space-time interactions with fixed spatial (<5 km) and temporal (<1 year) thresholds.
- Incorporated birth addresses and diagnosis locations, and used nearest neighbour distances.
- Employed a second-order analysis using K-functions for comprehensive assessment.
Main Results:
- Highly significant space-time clustering was observed, particularly for all leukaemias (0-14 and 0-4 years) and acute lymphoblastic leukaemia (ALL) (0-4 years) based on birth address and diagnosis time.
- Analyses using diagnosis location showed some significance but generally larger P-values.
- An excess of male cases was noted in space-time pairs, suggesting potential sex-based differences in susceptibility.
Conclusions:
- The findings strongly support an infectious aetiology for childhood leukaemia.
- Observed clustering patterns provide a foundation for future research into specific infectious agents.
- Sex-based differences in susceptibility to infection may influence leukaemia development.