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.