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

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident 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 (northern 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 pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20-84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater.

Results: During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107-109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases 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 cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

Keywords: Cardiovascular disease; Kidney cancer; PFAS; PFOA; PFOS; Perfluoroalkyl substances; Polyfluoroalkyl substances; Testicular cancer.

Fig. 1

Map of concentrations (ng/L) of perfluorooctanoic acid (PFOA) (top panels A and B) and perfluorooctanesulfonic acid (PFOS) (bottom panels C and D) in the surface water (left panels A and C) and groundwater (right panels B and D) of the municipalities of the Veneto Region (northern Italy). A red outline indicates the Red area. July 2013–June 2015. Source: Environmental Prevention and Protection Agency of the Veneto Region (ARPAV) (https://www.arpa.veneto.it/dati-ambientali/open-data/idrosfera/concentrazione-di-sostanze-perfluoroalchiliche-pfas-nelle-acque-prelevate-da-arpav. Accessed 14 Feb 2024)

Fig. 2

Lexis diagram showing the age groups, the calendar periods and –highlighted in gray– the birth cohorts considered in the analysis

Fig. 3

Cumulative standardised mortality ratio (SMR) for all causes by sex and birth cohort (1905–1984) in the perfluoroalkyl and polyfluoroalkyl substances (PFAS)-contaminated Red area. Panel (A), males; panel (B), females. The grey area indicates the 90% confidence band. The red line indicates the reference value. The Red area includes the 30 municipalities in the provinces of Vicenza, Padua and Verona (northern Italy) connected to the PFAS-contaminated aqueduct

Fig. 4

Cumulative standardised mortality ratio (SMR) for malignant neoplasms by sex and birth cohort (1905–1984) in the perfluoroalkyl and polyfluoroalkyl substances (PFAS)-contaminated Red area. Panel (A), males; panel (B), females. The grey area indicates the 90% confidence band. The red line indicates the reference value. The Red area includes the 30 municipalities in the provinces of Vicenza, Padua and Verona (northern Italy) connected to the PFAS-contaminated aqueduct

Fig. 5

Standardised mortality ratio (SMR) for cardiovascular disease by sex and calendar period in the perfluoroalkyl and polyfluoroalkyl substances (PFAS)-contaminated Red area. Red, males; green, females. Panel (A), Red area; panel (B), Red area A. The Red area includes the 30 municipalities in the provinces of Vicenza, Padua and Verona (northern Italy) connected to the PFAS-contaminated aqueduct. The Red area A includes the subset of 13 municipalities with PFAS contamination of the groundwater too. 1980–2018

Fig. 6

Standardised mortality ratio (SMR) for kidney cancer by sex and calendar period in the perfluoroalkyl and polyfluoroalkyl substances (PFAS)-contaminated Red area. Red, males; green, females. Panel (A), Red area; panel (B), Red area A. The Red area includes the 30 municipalities in the provinces of Vicenza, Padua and Verona (northern Italy) connected to the PFAS-contaminated aqueduct. The Red area A includes the subset of 13 municipalities with PFAS contamination of the groundwater too. 1980–2018