USC Researchers Receive $7.5 Million to Investigate PFAS Links to Liver and Endometrial Cancer
Researchers at the Keck School of Medicine of USC and the USC Norris Comprehensive Cancer Center have received two National Institutes of Health R01 grants totaling $7.5 million to investigate whether exposure to per- and polyfluoroalkyl substances, or PFAS, contributes to the development of liver and endometrial cancers. Awarded less than six months apart, the five-year grants will support what researchers describe as the first major studies designed specifically to examine PFAS as a potential driver of both malignancies. The projects will combine population-based research with laboratory experiments to determine not only whether exposure is associated with cancer risk, but also how these persistent chemicals may alter human biology before disease becomes clinically detectable.
PFAS are a large family of synthetic chemicals used for decades in products designed to resist water, oil, grease, stains and heat. They have been incorporated into nonstick cookware, food packaging, stain-resistant textiles and numerous industrial materials. Their carbon-fluorine bonds are exceptionally strong, allowing many PFAS compounds to remain in the environment for years or decades. Some can also persist in the human body, where repeated low-level exposure may lead to accumulation over time. PFAS have been detected in the blood of nearly all people tested in the United States and in approximately half of the nation’s public drinking-water systems. Although studies have linked exposure to immune disruption, metabolic disease, liver injury, kidney disease and several cancers, scientists still lack a complete understanding of the molecular pathways involved.
The grants are led by V. Wendy Setiawan, PhD, the Jane and Kris Popovich Chair in Cancer Research and a professor of population and public health sciences and medicine at the Keck School of Medicine. Vaia Lida Chatzi, MD, PhD, a professor of population and public health sciences and pediatrics, deputy director of the Southern California Environmental Health Sciences Center and director of the Southern California Superfund Research and Training Program for PFAS Assessment, Remediation and Prevention Center, is serving as a principal co-investigator. Their teams will examine PFAS exposure in relation to cancer development before diagnosis, an approach that can reduce a major source of uncertainty in environmental epidemiology: the possibility that disease or treatment changes a person’s exposure after the cancer has already emerged.
The first project, funded by a $3.4 million NIH award in March 2026, will focus on hepatocellular carcinoma, or HCC, the most common form of primary liver cancer. HCC accounts for approximately 80% of liver cancers and has a five-year survival rate of about 22%. Historically, chronic hepatitis B and hepatitis C infections were central causes of HCC in many populations. Vaccination, antiviral treatment and improved infection control have reduced the burden of viral hepatitis in some settings, while metabolic conditions such as obesity, type 2 diabetes and metabolic dysfunction-associated steatotic liver disease have become increasingly important contributors to liver cancer risk. Researchers now want to determine whether PFAS exposure may be another factor in this changing disease pattern.
The biological rationale for the liver cancer study comes from previous evidence that some PFAS compounds can affect lipid metabolism and promote fat accumulation in liver cells. Persistent exposure may also influence oxidative stress, inflammatory signaling, insulin regulation and gene-expression networks involved in cell growth and tissue repair. These processes are relevant to the progression from fatty liver disease to fibrosis, cirrhosis and, in some patients, cancer. The USC researchers will investigate whether mixtures of PFAS intensify these effects and whether specific molecular signatures can identify people whose liver tissue is more vulnerable. Because people are typically exposed to multiple PFAS compounds rather than a single chemical, the study will examine combinations and dose patterns intended to better reflect real-world conditions.
A central component of the liver cancer project will use data and biological samples from the Multiethnic Cohort Study, a long-running prospective investigation that has followed participants in Southern California and Hawaii for more than 25 years. The cohort includes people from diverse racial and ethnic backgrounds and contains blood samples collected before participants developed disease. Investigators will compare prediagnostic PFAS concentrations in participants who later developed HCC with exposure levels in comparable participants who did not. Measuring chemicals before diagnosis helps avoid reverse causation and recall bias, problems that can affect studies relying on samples collected after cancer is detected. The researchers will also use human liver spheroids, three-dimensional laboratory models grown from donor cells, to test how different PFAS mixtures affect liver structure, metabolism and cancer-related signaling.
The second project, supported by a $4.1 million NIH R01 grant awarded in June 2026, will examine PFAS and endometrial cancer. This cancer begins in the lining of the uterus and is the most common gynecologic cancer in the United States. Incidence has increased for at least a decade, with diagnoses occurring at younger ages in some populations. The study will include prediagnostic blood samples from 600 women who later developed endometrial cancer and 1,200 matched controls who did not. Samples will come from both the Multiethnic Cohort Study and the Southern Community Cohort Study, which includes participants from the southeastern United States. The combined dataset is expected to provide greater statistical power and broader representation than previous investigations of environmental chemicals and endometrial cancer.
Endometrial cancer is strongly influenced by hormonal and metabolic factors, including prolonged exposure to estrogen that is not balanced by progesterone, obesity, insulin resistance and diabetes. PFAS may interact with these pathways because some compounds can affect lipid metabolism, inflammation, endocrine signaling and immune function. The USC team will analyze whether individual PFAS chemicals or chemical mixtures are associated with elevated risk and whether associations differ according to body composition, metabolic health or reproductive history. Researchers will also study the social and environmental conditions surrounding exposure. Neighborhood characteristics, household income and access to fresh food may influence both PFAS contact and cancer susceptibility. Women living in food deserts, for example, may rely more heavily on packaged or fast food, increasing contact with food containers and wrappers that can contain PFAS while also contributing to diets associated with obesity and metabolic disease.
Together, the projects reflect a broader shift in cancer research toward studying environmental exposures as part of complex, interacting disease pathways. Rather than treating PFAS as an isolated cause, the researchers will assess how persistent chemicals may combine with genetics, metabolism, neighborhood conditions, diet and other exposures to alter cancer risk. The work will also connect epidemiological associations with laboratory evidence, allowing investigators to test whether patterns observed in human populations correspond to measurable changes in cells and tissues. If the studies identify consistent links and biological mechanisms, the findings could support policies aimed at reducing PFAS contamination, improving exposure monitoring and protecting communities that face disproportionate environmental risks. Preliminary data for the grants were supported by the NIEHS P30 Southern California Environmental Health Sciences Center and the USC Center for Translational Exposomics Research.
Subject of Research: PFAS exposure and its potential role in the development of hepatocellular carcinoma and endometrial cancer.
Article Title: USC Researchers Receive $7.5 Million to Investigate PFAS Links to Liver and Endometrial Cancer
Web References: Keck School of Medicine of USC: https://keck.usc.edu/; V. Wendy Setiawan: https://keck.usc.edu/faculty-search/veronica-w-setiawan/; Vaia Lida Chatzi: https://keck.usc.edu/faculty-search/vaia-lida-chatzi/; Southern California Environmental Health Sciences Center: https://scehsc.org/about; Southern California Superfund Research and Training Program for PFAS Assessment, Remediation and Prevention Center: https://sharpcenter.usc.edu/; USC Center for Translational Exposomics Research: https://keck.usc.edu/cter/
References: National Institutes of Health R01 grants; Multiethnic Cohort Study; Southern Community Cohort Study; NIEHS P30 Southern California Environmental Health Sciences Center; USC Norris Comprehensive Cancer Center.
Keywords: PFAS, forever chemicals, per- and polyfluoroalkyl substances, liver cancer, hepatocellular carcinoma, endometrial cancer, environmental health, cancer epidemiology, toxicology, public health, USC, NIH, exposomics, environmental exposure, metabolic disease
