BACKGROUND AND AIM: Childhood cancer incidence is known to vary by age, sex, and race/ethnicity, but evidence is limited regarding external risk factors. We aim to identify harmful combinations of air pollutants and other environmental and social risk factors in association with the incidence of childhood cancer based on 2003-2017 data from the Georgia Cancer Registry. METHODS: We calculated the standardized incidence ratios (SIR) of Central Nervous System (CNS) tumors, leukemia and lymphomas based on age, gender and ethnic composition in each of the 159 counties in Georgia, USA. County-level information on eight carcinogenic air pollutants (benzene, trichloroethylene, ethylene-oxide, formaldehyde, pentachlorophenol, styrene, tetrachloroethylene, 1,3-butadiene), socioeconomic status, tobacco smoking, alcohol drinking and obesity were derived from US EPA and other public data sources. We applied an unsupervised learning tool (self-organizing map, SOM) to identify pertinent types of multi-exposure combinations. Spatial Bayesian Poisson models (Leroux-CAR) were fit with indicators for each multi-exposure category as exposure and SIR of childhood cancers as outcomes. RESULTS:Based on county-level information of external risk factors, the SOM algorithm divided the state of Georgia into 5 distinct clusters (clusters 4-5 comprising metropolitan/urban areas). Mean SIR ranged from 0.8 (rural-cluster-1) to 1.1 (urban-cluster-5) for leukemia, 1.0 (rural-cluster-3) to 1.4 (rural-cluster-1) for lymphomas and 1.5 (rural-cluster-1) to 1.8 (urban-cluster-4) for CNS tumors. Children living in urban counties characterized by higher air pollution concentrations and proportions of alcohol drinking (urban-cluster-4) had higher SIR of childhood leukemia and lymphomas than children living in rural-cluster-1 (risk ratio [95%-credible intervals]: 1.3 [1.0,1.6]) and rural-cluster-3 (1.2 [1.0, 1.4]), respectively. We found no significant associations for spatial variation of CNS tumors. CONCLUSIONS:We found spatial clustering of childhood cancer in counties with higher air pollution concentrations and larger proportions of alcohol drinking. More research is needed to identify the causal risk factors for these associations. KEYWORDS: Air pollution, Cancer and cancer precursors, Children's environmental health, Socio-economic factors, Multi-pollutant, Environmental epidemiology
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