Environmental, social and behavioral risk factors in association with spatial clustering of childhood cancer incidence

Abstract

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. 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 air pollution, socioeconomic status (SES), tobacco smoking, alcohol drinking and obesity were derived from US EPA and other public data sources. We applied two unsupervised learning tools (self-organizing map [SOM] and exposure-continuum mapping [ECM]) 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. We identified consistent associations of environmental (pesticide exposure) and social/behavioral stressors (low socioeconomic status, alcohol) with spatial clustering of pediatric cancer class II (lymphomas and reticuloendothelial neoplasms), but not for other cancer classes. More research is needed to identify the causal risk factors for these associations.

Fig. 1.. Distribution of pediatric cancer cases in Georgia (SIR).

Histogram of the Standardized Incidence Rate for A. class I cancers, B. class II cancers and C. class III cancers. County-level SIR map of D. class I cancers, E. class II cancers and F. class III cancers. Cancer types grouped according to the International Classification of Childhood Cancer (ICCC): Class I: Leukemias, Myeloproliferative and Myelodysplastic Diseases; Class II Lymphomas and Reticuloendothelial Neoplasms; Class III CNS and Miscellaneous Intracranial and Intraspinal Neoplasms.

Fig. 2.. Self-organizing maps (SOM).

Exposure clusters in association with increased SIR of the three most common classes of cancer. A. SOM cluster star plot, slices represent median values of a mixture component, each circle is a SOM cluster. B. Map of counties in Georgia colored by SOM cluster. C–E. Results of the Leroux CAR models for the association between SOM cluster membership and SIR of pediatric cancer (C. Class I, D. Class II, E. Class III). Cluster 4 was used as the reference group because it had the lowest levels of adverse risk factors (compare panel A). Cancer types grouped according to the International Classification of Childhood Cancer (ICCC): Class I Leukemias, Myeloproliferative and Myelodysplastic Diseases; Class II Lymphomas and Reticuloendothelial Neoplasms; Class III CNS and Miscellaneous Intracranial and Intraspinal Neoplasms. As the distribution of the SIR of cancer class II showed zero-inflation, we used Leroux CAR models with zero-inflated Poisson distribution for associations with cancer class II.

Fig. 3.. Exposure-continuum mapping (ECM).

Exposure patterns in association with increased SIR of the three most common types of cancer. A. Exposure continuum map. Slices represent median values of a mixture component; each circle is an ECM cluster. Relative frequencies (%) are provided on the bottom of each cluster. B–D. The estimated joint-dose response function that illustrates the association between SIR of pediatric cancer (B. class I, C. class II, D. class III) and location on our exposure continuum map. Cancer types grouped according to the International Classification of Childhood Cancer (ICCC): Class I Leukemias, Myeloproliferative and Myelodysplastic Diseases; Class II Lymphomas and Reticuloendothelial Neoplasms; Class III CNS and Miscellaneous Intracranial and Intraspinal Neoplasms.

Fig. 4.

Spatial distribution of the Georgia counties assigned to the four ECM clusters (clusters 1,2,5 and 6, compare Fig. 3) with the highest SIR of cancer class II (Lymphomas and Reticuloendothelial Neoplasms).