All-cause, circulatory disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980-2018)

Background Perfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. A clear association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (north-eastern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. Methods The Italian National Institute of Health and the Italian National Institute of Statistics made available the anonymous records of death certificates of residents of the provinces of Vicenza, Verona and Padova (males, n=29,629; females, n=29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardized (European standard population 2013) mortality ratios using the total population of the three provinces in the same calendar period as a reference. The birth cohort analysis was performed using cumulative risks for ages 20-84 years. Results During the 33 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of available cause-specific mortality), in the resident population of the Red area (the municipalities being connect to the contaminated water plant) we observed 51,621 deaths as compared to 47,731 expected (age-sex SMR: 108; 90% CI: 107-109). We found evidence of raised mortality for diseases of the circulatory system (in particular, heart disease and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. Conclusions For the first time, an association of PFAS exposure with mortality from circulatory disease mortality was formally demonstrated. Circumstantial evidence regarding kidney cancer and testicular cancer is consistent with previously reported data. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was partially funded by the Veneto Regional Administration (DGR 1495/2019, DDR 30/2020, Resolution AULSS8 1402/2020) by committing a professional assignment to the Giulio A. Maccacaro Epidemiology & Prevention Society. The authors received no funding. The authors retained full control over the manuscript and full intellectual freedom to report and interpret the results. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethics Committee at the Romagna Cancer Institute (ID: IRST100.37). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Research data are available from Giada Minelli (contact email:giada.minelli@iss.it) upon reasonable request