Per- and polyfluoroalkyl substances levels other than PFOS, PFOA, or PFHxS and liver cancer risk: a nested case-control analysis

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ID: 328605
2026
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Abstract
Abstract Epidemiologic studies of PFAS and liver cancer risk have produced conflicting results with no strong or clear associations for pre-diagnostic perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS). We now report analyses of nine additional PFAS in a nested case-control study within 12 prospective cohorts (853 cases, 853 matched controls) in the United States. Using multivariable-adjusted conditional logistic regression, we estimated odds ratios per 90th vs. 10th percentile increase in PFAS levels. Perfluoroheptanoic acid (PFHpA) was positively associated with liver cancer risk (OR: 1.78, 95% CI: 1.26–2.52); no associations were observed for other PFAS. Significant heterogeneity was observed by sex, cancer subtype, and time from blood collection. Associations were stronger among males (OR: 3.72, 95% CI: 2.10–6.59), for hepatocellular carcinoma (4.53, 2.59–7.94), and for those diagnosed ≤10 years after blood collection (3.17, 1.80–5.57). Given continued use of short-chain PFAS in consumer products, further research on their effects on liver health is warranted.
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Authors Cody Z. Watling, Jessica L. Petrick, Barry I. Graubard, Hyokyoung G. Hong, Xuehong Zhang, Matthew J Barnett, Mollie E. Barnard, Yu Chen, A Heather Eliassen, J Michael Gaziano, Wen‐Yi Huang, Jae H Kang, Jill Koshiol, I-Min Lee, Erikka Loftfield, Steven C Moore, Lorelei A Mucci, Marian L Neuhouser, Christina C. Newton, Howard D Sesso, Martha Shrubsole, Rashmi Sinha, Lesley Tinker, Triplette Matthew, Caroline Y. Um, Kala Visvanathan, Jean Wactawski‐Wende, Eleanor L. Watts, Walter C Willett, Fen Wu, Wei Zheng, Peter T. Campbell, Jonathan N Hofmann, Mark P. Purdue, Dinesh Barupal, Katherine A. McGlynn
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Journal JNCI Journal of the National Cancer Institute
Year 2026
DOI
10.1093/jnci/djag325
URL
https://doi.org/10.1093/jnci/djag325
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