Per- and polyfluoroalkyl substances levels other than PFOS, PFOA, or PFHxS and liver cancer risk: a nested case-control analysis
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.
Authors
- Hyokyoung G. Hong (ORCID: https://orcid.org/0000-0002-4280-6243)
- Eleanor L. Watts (ORCID: https://orcid.org/0000-0001-9229-2589)
- Jean Wactawski‐Wende (ORCID: https://orcid.org/0000-0003-3096-9595)
- Jessica L. Petrick (ORCID: https://orcid.org/0000-0001-6580-450X)
- Mark P. Purdue (ORCID: https://orcid.org/0000-0003-1177-3108)
- Christina C. Newton (ORCID: https://orcid.org/0000-0003-1471-5608)
- Katherine A. McGlynn (ORCID: https://orcid.org/0000-0003-2329-9933)
- Erikka Loftfield (ORCID: https://orcid.org/0000-0002-3573-8748)
- Triplette Matthew
- Fen Wu (ORCID: https://orcid.org/0000-0002-0563-5887)
- Peter T. Campbell (ORCID: https://orcid.org/0000-0002-5549-2036)
- Barry I. Graubard (ORCID: https://orcid.org/0000-0002-6787-1105)
- Mollie E. Barnard (ORCID: https://orcid.org/0000-0002-4843-4655)
- DINESH BARUPAL
- Cody Z. Watling (ORCID: https://orcid.org/0000-0002-6643-9660)
- Caroline Y. Um (ORCID: https://orcid.org/0000-0001-5449-6230)
- Xuehong Zhang (ORCID: https://orcid.org/0000-0002-8260-8508)
- Wen‐Yi Huang (ORCID: https://orcid.org/0000-0002-4440-3368)
- Matthew J Barnett
- Jonathan N Hofmann
- Martha Shrubsole
- Rashmi Sinha
- Jill Koshiol
- Lesley Tinker
- Jae H Kang
- Steven C Moore
- Kala Visvanathan
- J Michael Gaziano
- I-Min Lee
- Wei Zheng
- Marian L Neuhouser
- Walter C Willett
- A Heather Eliassen
- Lorelei A Mucci
- Yu Chen
- Howard D Sesso
Institutions
- Boston University (US)
- Brigham and Women's Hospital (US)
- American Cancer Society (US)
- Albert Einstein College of Medicine (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Johns Hopkins University (US)
- Vanderbilt University (US)
- VA Boston Healthcare System (US)
- Yale University (US)
- Fred Hutch Cancer Center (US)
- Yale New Haven Health System (US)
- National Cancer Institute (US)
- Vanderbilt Health (US)
- Division of Cancer Epidemiology and Genetics
- New York University (US)
- University at Buffalo, State University of New York (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- JNCI Journal of the National Cancer Institute
- Published
- 2026-09-17
- DOI
- https://doi.org/10.1093/jnci/djag325
- Primary Topic
- Per- and polyfluoroalkyl substances research
- Type
- article
- Field-Weighted Citation Impact
- 0.00