Pesticides and risk of pancreatic adenocarcinoma in France: a nationwide spatiotemporal ecological study between 2011 and 2021.

While pancreatic adenocarcinoma (PA) incidence is increasing, especially in France, the association between pesticides and PA remains unclear. The aims of this study were to assess the spatiotemporal distribution of the incidence of PA in France between 2011 and 2021 and to determine whether pesticide exposure was associated with higher risk of PA. We employed a disease-mapping and ecological regression approach with medicoadministrative data covering 99% of the French population. Exposure data were drawn from an open purchase database. A pesticide exposure intensity index (PEXI), defined as the logged and scaled median of the ratio quantity of substance over agricultural surface per spatial unit was used for total quantity (total PEXI) and 9 specific substances. The analyses were adjusted for tobacco-induced diseases, deprivation, community medicine accessibility, alcohol-related disease and morbid obesity. A Bayesian hierarchical spatiotemporal model was used to both model the incidence over time and space, and to estimate the risk of PA for pesticide use. We identified 134 102 incident cases of PA between 2011 and 2021. The relative risk of PA was heterogeneous across space with greater risk around Paris, central France and the Mediterranean coast. We observed an association, albeit small, between the total PEXI and PA incidence over the study period (RR: 1.0130; CI95% [1.0057;1.0204]). Sulphur for spraying, mancozeb, and glyphosate showedevidence of an association of the same magnitude. These findings show that new cases of PA occur heterogeneously in space, raising questions about our understanding of PA environmental risk factors. The association with pesticide exposure should be confirmed and underlying mechanisms understood using individual-level studies.