Geographic Patterns of Pancreatic Cancer Mortality and Dietary Microplastic Exposure in Italy: An Ecological Hypothesis-Generating Framework

Pancreatic cancer (PC) mortality in Italy exhibited a persistent North–South macro-geographic gradient between 2003 and 2022, with significantly higher rates in northern regions. Whilst traditional risk factors partially explain this trend, the contribution of emerging dietary xenobiotics remains unexplored. This study presents an integrated ecological and ecotoxicological modelling framework combining long-term mortality rates, household dietary intake from ISTAT registries, and micro- and nanoplastic (MNP) exposure derived from the FOMIC-Py pyramid. Using robust linear models with 5000-iteration bootstrap validation, we identified dietary fibre as a robust, independent protective factor against PC mortality. Conversely, higher regional reliance on packaged foods coupled with industrial airborne plastic deposition yields a 58.4% higher estimated annual MNP exposure in Northern Italy compared to Southern cohorts. Mechanistically, ingested plastics crossing the intestinal barrier can bioaccumulate in pancreatic tissue, inducing chronic oxidative stress, inflammation, and cellular dysfunction. Although ecological limitations preclude direct causality, this predictive exposure model establishes dietary plastics as plausible environmental cofactors modulating PC geographic disparities. These key findings highlight the dual importance of promoting high-fibre diets and mitigating single-use plastic exposure within food supply chains to address these emerging environmental cancer risks across European population cohort studies.