REVIEW article
Front. Toxicol.
Sec. Clinical Toxicology
Impact of PFAS exposure on lipid metabolic pathways: Mechanisms and implications in carcinogenesis
Provisionally accepted
- Markey Cancer Center and Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, United States
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Per-and polyfluoroalkyl substances (PFAS) are a large class of synthetic chemicals widely used in industrial and consumer products owing to their unique surfactant properties. Their environmental persistence and bioaccumulative nature have resulted in widespread contamination of water, soil, and food sources, raising significant concerns for human health. Epidemiological and toxicological studies increasingly associate PFAS exposure with elevated risks of cancers, including liver, kidney, breast, and testicular cancers; however, the mechanisms underlying these associations remain incompletely understood. One emerging explanation is that PFAS disrupt lipid metabolism, a pathway frequently reprogrammed during cancer initiation and progression. PFAS share structural similarities with endogenous fatty acids and can bind to lipid transport proteins and/or activate lipid-sensitive nuclear receptors. Current evidence indicates that PFAS exposure is associated with increased blood lipid levels, as well as dysregulation of key transcription factors—such as peroxisome proliferator-activated receptors and sterol regulatory element-binding proteins—that can link PFAS exposure to tumor-promoting metabolic alterations. These disruptions can impair dietary fatty acid uptake and de novo lipid synthesis, leading to abnormal lipid accumulation, oxidative stress, and activation of pro-oncogenic signaling pathways. The purpose of this review is to synthesize current evidence on how PFAS exposure contributes to carcinogenesis through the disruption of lipid metabolism. By integrating findings from population studies, mechanistic research, and molecular insights, this review highlights lipid dysregulation as a critical connection between PFAS exposure and cancer biology and underscores the need for deeper investigation into this pathway.
Keywords: Cancer2, carcinogenesis5, forever chemicals3, Lipid metabolism4, PFAS exposure1
Received: 15 Dec 2025; Accepted: 26 Jan 2026.
Copyright: © 2026 Ferguson, Tessmann and Zaytseva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yekaterina Y Zaytseva
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