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PFAS and liver cancer: linking epidemiological evidence with mechanistic studies

Award Number: R01CA300355
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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PFAS and liver cancer: linking epidemiological evidence with mechanistic studies - ABSTRACT Hepatocellular carcinoma (HCC) is the most common form of liver cancer, and has a dismal five-year survival rate of 22%, making it one of the most fatal cancers. While hepatitis virus-related HCC is declining, the incidence of non-viral metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC is rising and is projected to become the leading cause of liver cancer. Growing evidence suggests that environmental chemical exposures contribute to liver cancer risk by promoting chronic inflammation, fibrosis, and metabolic dysfunction, yet these factors remain underexplored. Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals and have emerged as potential risk factors for liver damage. However, their impact on the etiology of MASLD and HCC remains largely unexplored. In response to PAR-22-083 “Epidemiologic Research on Emerging Risk Factors and Liver Cancer Susceptibility”, we propose the first translational study to investigate PFAS as novel risk factors for HCC by integrating population-based research with in vitro experiments. Leveraging comprehensive epidemiological data spanning over two decades and pre-diagnostic plasma samples in the Multiethnic Cohort Study (MEC), we aim to elucidate the impact of PFAS exposure on MASLD and HCC risks. Additionally, using in vitro experiments with 3D human liver spheroids, 2D HepG2 cell cultures, and various omics techniques we will explore the biological pathways linking PFAS exposure to liver steatosis and HCC development. To enhance precision, high-dimensional machine learning methods will be employed to construct risk profiles for HCC based on PFAS plasma concentrations, multi-omics data, and genetic factors, offering new insights into personalized prevention strategies. Our specific aims are: 1) to evaluate associations between individual PFAS and PFAS mixtures in pre-diagnostic plasma samples with MASLD and HCC risk and examine whether genetic predisposition modifies the associations; 2) to examine the biological pathways underlying PFAS-induced liver steatosis and HCC using in vitro studies and single-cell omics; 3) to construct precise risk profiles of HCC based on PFAS plasma concentrations, genetics and multi-omics data. By combining epidemiological, mechanistic, and bioinformatics analyses, this study will provide critical insights into the role of environmental chemicals in HCC development. Our findings will inform policies to minimize PFAS exposure, reduce the burden of HCC, and identify potential targets for prevention and intervention strategies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $681,676 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	1	3/6/2026	NEW	$681,676
														Subtotal = $681,676

Grand Total All Awards = $681,676

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PFAS and liver cancer: linking epidemiological evidence with mechanistic studies

Award Number: R01CA300355

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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