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. 2025 May;35(3):425-436.
doi: 10.1038/s41370-024-00742-2. Epub 2025 Jan 9.

Associations between per-and polyfluoroalkyl substances (PFAS) and county-level cancer incidence between 2016 and 2021 and incident cancer burden attributable to PFAS in drinking water in the United States

Shiwen Li  1 , Paulina Oliva  2 , Lu Zhang  3 , Jesse A Goodrich  3 , Rob McConnell  3 , David V Conti  3 , Lida Chatzi  3 , Max Aung  3
Affiliations

Associations between per-and polyfluoroalkyl substances (PFAS) and county-level cancer incidence between 2016 and 2021 and incident cancer burden attributable to PFAS in drinking water in the United States

Shiwen Li et al. J Expo Sci Environ Epidemiol. 2025 May.

Abstract

Background: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked with various cancers. Assessment of PFAS in drinking water and cancers can help inform biomonitoring and prevention efforts.

Objective: To screen for incident cancer (2016-2021) and assess associations with PFAS contamination in drinking water in the US.

Methods: We obtained county-level age-adjusted cancer incidence (2016-2021) from the Surveillance, Epidemiology, and End Results (SEER) Program. Data on PFAS levels in public drinking water systems were obtained from the Third (UCMR3; 2013-2015) and Fifth (UCMR5; 2023-2024) Unregulated Contaminant Monitoring Rule. UCMR3 measured PFOS, PFOA, PFNA, PFHxS, PFHpA, and PFBS. UCMR5 expanded measurements to include PFBA, PFHxA, PFPeA, and PFPeS. We created indicators of PFAS detection and, for UCMR5, concentrations above Maximum Contaminant Levels (MCLs). MCLs for PFOA and PFOS are 4 ng/L, and for PFNA and PFHxS are 10 ng/L. We used Poisson regression models to assess associations between PFAS detection or MCL violation and cancer incidence, adjusting for potential confounders. We estimated the number of attributable cancer cases.

Results: PFAS in drinking water was associated with increased cancer incidence in the digestive, endocrine, oral cavity/pharynx, and respiratory systems. Incidence rate ratios (IRRs) ranged from 1.02 to 1.33. The strongest association was observed between PFBS and oral cavity/pharynx cancers (IRR: 1.33 [1.04, 1.71]). Among males, PFAS was associated with cancers in the urinary, brain, leukemia, and soft tissues. Among females, PFAS was associated with cancers in the thyroid, oral cavity/pharynx, and soft tissue. PFAS in drinking water is estimated to contribute to 4626 [95% CI: 1,377, 8046] incident cancer cases per year based on UCMR3 data and 6864 [95% CI: 991, 12,804] based on UCMR5.

Impact statement: The ecological study examined the associations between PFAS in drinking water measured in two waves (2013-2015 and 2023-2024) and cancer incidence between 2016 and 2021. We found that PFAS in drinking water was associated with cancers in the organ system including the oral cavity/pharynx, lung, digestive system, brain, urinary system, soft tissue, and thyroid. Some cancers have not been widely studied for their associations with PFAS. We also observed sex differences in the associations between PFAS and cancer risks. This is the first ecological study that examined PFAS exposure in drinking water and various cancer risks.

Keywords: Cancer; Drinking Water; PFAS.

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Conflict of interest statement

Competing interests: The authors declare the following financial interests/personal relationships which may be considered potential competing interests: LC has served as an expert consultant for plaintiffs in litigation related to PFAS-contaminated drinking water. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics approval and consent to participate: All study protocols were reviewed and approved by the University of Southern California Institutional Review Board (UP-24-00198). Informed consent was waived (determined by the Institutional Review Board) per 45 CFR 46.102 (e)(1), as the project does not include information or biospecimens obtained through intervention or interaction with the individuals, and does not use, study, or analyze information or biospecimens or does not obtain, use, study, analyze, or generate identifiable private information or identifiable biospecimens.

Figures

Fig. 1
Fig. 1. Illustration of the distribution of PFAS in drinking water and annual average cancer incidence between 2016 and 2021.
A Detection of PFOA in drinking water based on UCMR3, B Maximum Contaminant Level (MCL) violation of PFOA based on UCMR5, C Annual average cancer incidence rate per 100,000 (between 2016 and 2021) for cancers in the respiratory system, and D Annual average cancer incidence rate per 100,000 (between 2016 and 2021) for cancers in the endocrine system.
Fig. 2
Fig. 2. Associations between annual average county-level age-adjusted cancer incidence rate (per 100,000 persons per year) between 2016 and 2021 and detection or Maximum Contaminant Level (MCL) violation of per- and polyfluoroalkyl substances (PFAS) in drinking water based on UCMR3.
For UCMR3, all PFAS were categorized into detected/not detected. The lines for statistically significant results are shown in blue.
Fig. 3
Fig. 3. Associations between annual average county-level age-adjusted cancer incidence rate (per 100,000 persons per year) between 2016 and 2021 and detection or Maximum Contaminant Level (MCL) violation of per- and polyfluoroalkyl substances (PFAS) in drinking water based on UCMR5.
For UCMR5, all PFAS were categorized into Detected/Not Detected except for PFOS, PFOA, PFHxS, and PFNA which were categorized into above Maximum Contaminant Level or Not (4 ng/L for PFOS and PFOA and 10 ng/L for PFHxS and PFNA). The lines for statistically significant results are shown in red.
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