Environment/Climate Change
Association between Per- and Polyfluoroalkyl Substances and Liver Cancer Risk Xinyuan Zhang* Xinyuan Zhang Longgang Zhao Howard D. Sesso I-Min Lee Julie E. Buring Michelle Lai Philippe Grandjean Xuehong Zhang
Background
Liver cancer incidence in the US has tripled since the 1980s. The underlying causes likely include exposures from environmental toxins with carcinogenicity, e.g., per- and polyfluoroalkyl substances (PFASs) to which US populations are ubiquitously exposed. We aimed to study circulating levels of PFAS in nested case-control studies comparing liver cancer cases to both generally healthy controls and liver disease controls.
Methods
We identified 44 liver cancer cases from the Women’s Health Study and the Physicians’ Health Study, with 1:1 cancer-free controls matched by age, sex, and time of blood collection. We also identified 66 liver cancer cases from the Mass General Brigham Biobank, with 1:1 cancer-free, metabolic dysfunction-associated steatotic liver disease (MASLD) controls matched by the same criteria. The stored pre-diagnostic blood samples were assayed for major PFASs. We examined the associations of total and individual PFASs with liver cancer risk by comparing tertiles and comparing >90th versus <90th percentile using conditional logistic regression models, adjusting for smoking status, alcohol intake, obesity, and diabetes.
Results
Compared to healthy controls, the highest vs. lowest tertile of total PFAS was not significantly different for the risk of liver cancer (adjusted OR=1.09 (95%CI: 0.28-4.28). However, those at or above the 90th percentile of perfluorodecanoic acid (adjusted OR=7.96 (95%CI: 1.09-58.4)) and perfluoroundecanoic acid (adjusted OR=10.5 (95%CI: 1.06-103)), compared to those <90th percentile, had a statistically significant higher risk of liver cancer. Compared to MASLD controls, adjusted models did not find significant associations between total or individual PFASs and liver cancer risk (all P>0.05).
Conclusion
Certain PFAS at high levels might be associated with liver cancer risk, although evidence from larger scale studies is warranted, potentially informing policy making and regulation of various PFASs in the US and worldwide.
