Nebraska’s age-adjusted incidence rates for childhood cancers are among the highest in the US. Previous studies indicated associations between agrichemical exposures (atrazine and nitrates) and pediatric cancer rate, assuming single pollutant exposure. We evaluated the joint association between the agricultural mixture and pediatric cancer. Agrichemical exposures at a county scale were quantified using the USGS Pesticide National Synthesis Project for frequently applied pesticides from 1992 to 2014 in 93 Nebraska counties. Outcomes were quantified using pediatric cancer diagnosed among children < 20 years of age (1992-2014) from the Nebraska cancer registry. We adjusted for social vulnerability factors such as race, income, employment, and access to care. The associations between 32 agrichemicals and cancer subtypes were assessed using the Generalized Weighted Quantile Sum Regression (gWQS) model. The model was fit assuming a Poisson distribution and using the pediatric population as an offset-term and social vulnerability factors as covariates. We observed a statistically significant positive association between the 32 agrichemicals and overall pediatric cancer and subtypes. The strength of associations was slightly stronger among brain and CNS cancers (β=0.36, CI = 0.14, 0.57) compared to overall cancer (β=0.30, CI = 0.16, 0.44) and leukemia (β=0.23, CI =0.09, 0.38). Dicamba, glyphosate, paraquat, quizalofop, triasulfuron, and tefluthrin largely contributed to the joint association. These findings may explain the joint associations of the agrichemical mixture on childhood cancer. Alternative biomarker-based approaches to measuring human exposure are worth investigating for chemicals of concern, particularly in counties with high agrichemical and cancer rates.

This study was conducted to examine, at the county level, the relationship between pediatric cancers incidence rate and atrazine and nitrate mean concentrations in surface and groundwater. A negative binomial regression analysis was performed to investigate the association between central nervous system (CNS) tumors, leukemia, lymphoma, and atrazine and nitrate mean concentrations in surface and groundwater. The age-adjusted brain and other CNS cancers incidence was higher than the national average in 63% of the Nebraska counties. After controlling for nitrate concentrations in surface and groundwater, counties with atrazine concentrations between 0.95 - 2.82 µg/L in both surface and groundwater had a higher incidence rate for pediatric cancers (brain and other CNS, leukemia, and lymphoma) compared to counties with surface and groundwater atrazine concentrations in the reference group (0.00 - 0.13 µg/L). Additionally, compared to counties with groundwater nitrate concentrations between 0 and 2 mg/L (reference group), counties with groundwater nitrate concentrations between 2.1 and 5 mg/L (group 2) had a higher incidence rate for pediatric brain and other CNS cancers (IRR=13.25; 95% CI: 13.00-13.50), leukemia (IRR=6.13; 95% CI: 6.02-6.26), and lymphoma (IRR=11.53; 95% CI: 11.32-11.75) after adjusting for all covariates in the model. While these findings do not indicate a causal relationship, they suggest that atrazine and nitrate may pose a significant risk relative to the genesis of pediatric brain and CNS cancers, leukemia, and lymphoma.