Introduction: The incidence of kidney cancer demonstrates significant geographic variation that suggests a role for environmental risk factors, in addition to genetic and clinical risk factors. We sought to evaluate associations between groundwater environmental exposures and kidney cancer incidence. Methods: We identified 180 constituents from 18,506 public groundwater wells in all 58 counties in California from 1996-2010. We obtained county-level kidney cancer incidence data from the California Cancer Registry from 2003-2017. Using an XWAS framework, which is the application of statistical approaches popularized in GWAS studies, we created a water-wide ecological association study (WWAS). We fit Poisson regression models to estimate the association between each constituent and county-level kidney cancer standardized incidence ratios, adjusting for known risk factors including sex, obesity, prevalence of smoking, and socioeconomic status at the county-level. Results: Eleven groundwater constituents met stringent WWAS criteria and were associated with kidney cancer incidence. The seven constituents that had a positive association with kidney cancer standardized incidence ratios were chlordane (relative risk (RR) = 1.06, 95%CI: 1.02 – 1.10), dieldrin (RR = 1.04, 95%CI: 1.01 – 1.07), 1,2-dichloropropane (RR = 1.04, 95%CI: 1.02 – 1.05), 2,4,5-TP (Silvex) (RR = 1.03, 95%CI: 1.01 – 1.05), glyphosate (RR = 1.02 95%CI: 1.01 – 1.04), endothall (RR = 1.02, 95%CI: 1.01– 1.03), and carbaryl (RR = 1.02, 95%CI: 1.01 – 1.03). The constituent with the strongest inverse association was bromide (RR = 0.96, 95%CI: 0.94 – 0.99). Conclusions: Eleven groundwater constituents met stringent WWAS criteria and were associated with kidney cancer incidence. The seven constituents that had a positive association with kidney cancer standardized incidence ratios were chlordane (relative risk (RR) = 1.06, 95%CI: 1.02 – 1.10), dieldrin (RR = 1.04, 95%CI: 1.01 – 1.07), 1,2-dichloropropane (RR = 1.04, 95%CI: 1.02 – 1.05), 2,4,5-TP (Silvex) (RR = 1.03, 95%CI: 1.01 – 1.05), glyphosate (RR = 1.02 95%CI: 1.01 – 1.04), endothall (RR = 1.02, 95%CI: 1.01– 1.03), and carbaryl (RR = 1.02, 95%CI: 1.01 – 1.03). The constituent with the strongest inverse association was bromide (RR = 0.96, 95%CI: 0.94 – 0.99). SOURCE OF Funding: None
