Enhanced spatial analysis assessing the association between PFAS-contaminated water and cancer incidence: rationale, study design, and methods

Background: Cancer is a complex set of diseases, and many have decades-long lag times between possible exposure and diagnosis. Environmental exposures, such as per- and poly-fluoroalkyl substances (PFAS) and area-level risk factors (e.g., socioeconomic variables), vary for people over time and space. Evidence suggests PFAS exposure is associated with several cancers; however, studies to date have various limitations. Few studies have used rigorous spatiotemporal approaches, and, to our knowledge, none have assessed cumulative exposures given residential histories or incorporated chemical mixture modeling. Thus, spatiotemporal analysis using advanced statistical approaches, accounting for spatially structured and unstructured heterogeneity in risk, can be a highly informative strategy for addressing the potential health effects of PFAS exposure. Methods: Using population-based incident cancer cases and cancer-free controls in a 12-county area of southeastern Pennsylvania, we will apply Bayesian spatiotemporal analysis methods using historically reconstructed PFAS-contaminated water exposure given residential histories, and other potential cancer determinants over time. Bayesian group index models enable assessment of various mixtures of highly correlated PFAS chemical exposures incorporating mobility/residential history, and contextual factors to determine the association of PFAS-related exposures and cancer incidence. Discussion: The purpose of this paper is to describe the Enhanced PFAS Spatial Analysis study rationale, study design, and methods.