Researchers at the Keck School of Medicine of USC and USC Norris Comprehensive Cancer Center have received two grants from the National Institutes of Health (NIH) totaling $7.5 million to study whether exposure to per- and polyfluoroalkyl substances (PFAS), the synthetic compounds known as "forever chemicals," increases the risk of liver cancer and endometrial cancer. The two R01 grants, awarded less than six months apart, will fund the first studies of their kind to investigate PFAS as a driver of these cancers.
PFAS are used in nonstick cookware, stain-resistant fabrics, food packaging and other everyday products. Because they break down very slowly, they accumulate in the environment and in the human body over time. They are now detected in the blood of nearly all U.S. residents and have been found in roughly half of the country's public drinking water supplies. Growing evidence links PFAS exposure to a range of health problems, including kidney disease, liver damage and several types of cancer. However, the biological mechanisms underlying many of those risks are still poorly understood.
It's deeply gratifying to be able to get these two grants. It's a validation that our research addresses important public health questions, with the potential for real-world impact."
V. Wendy Setiawan, PhD, study's principal investigator, the Jane and Kris Popovich Chair in Cancer Research and professor of population and public health sciences and medicine, Keck School of Medicine
Investigating rising liver cancer rates
In March 2026, the NIH awarded a five-year, $3.4 million grant to USC researchers to investigate PFAS as a potential risk factor for hepatocellular carcinoma (HCC) through a translational research approach. HCC is the most common form of liver cancer, accounting for roughly 80% of all liver cancers and carrying a five-year survival rate of 22%. With a translational research approach, the team's goal is to produce research that will inform policies to minimize PFAS exposure, reduce the cancer burden and find ways to help people who have been exposed to PFAS.
"We have been studying the effects of PFAS for years, particularly in relation to metabolic diseases such as obesity, diabetes and liver disease. It is becoming increasingly apparent that these chemicals may also play a role in the development of cancers. With these grants, we hope to better understand this relationship and identify the biological mechanisms that link PFAS exposure to cancer risk. " said the study's principal co-investigator Vaia Lida Chatzi, MD, PhD, professor of population and public health sciences and pediatrics at the Keck School of Medicine, 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.
In the past, most HCC cases were driven by hepatitis B and C infections. But as vaccines and antiviral treatments have reduced those cases, a new pattern has emerged: an increase in liver cancer linked to metabolic conditions, including obesity and fatty liver diseases. Based on laboratory evidence that some PFAS promote fat accumulation in liver cells and trigger cancer-related cellular changes, researchers suspect exposure to the chemicals may be a contributing factor.
What distinguishes this study is its combination of large-scale epidemiology with laboratory experiments. The research team will analyze data from the Multiethnic Cohort Study (MEC), a prospective study that has followed participants from Southern California and Hawaii for more than 25 years. MEC study data includes blood samples collected before participants developed disease. Because blood samples were collected before participants developed cancer, researchers can measure PFAS exposure before disease onset, helping reduce biases that can arise when exposure is assessed after diagnosis.
The team will also expose human liver spheroids, 3D models of the liver grown from donor cells, to multiple types of PFAS at varying doses, mimicking real-world combinations and exposure patterns, to reveal the biological pathways linking PFAS to liver disease and cancer.
Filling a gap in women's cancer research
Just three months later, in June 2026, Setiawan's team received a second R01 grant of $4.1 million over five years to fund what researchers believe is the largest prospective study to date examining PFAS and endometrial cancer risk.
Endometrial cancer is the most common gynecologic cancer in the United States. Rates have been rising for at least a decade, and diagnoses are occurring at younger ages.
The study will draw on pre-diagnostic blood samples from 600 women who later developed endometrial cancer and 1,200 matched controls. The samples will be pooled from both the MEC Study and the Southern Community Cohort Study, a large study of participants from the southeastern United States.
The research team will analyze how factors such as neighborhood, income and food access interact with PFAS exposure to influence cancer risk. For example, researchers suspect that where women live may shape their risk. Those living in food deserts, communities with limited access to fresh food, may rely more on fast-food packaging that contains PFAS, thus compounding their exposure.
A shared scientific vision
Although the two studies focus on different cancers, they share a common purpose.
"We want to understand how environmental exposures contribute to cancer development before the disease occurs," said Setiawan.
The two back-to-back awards reflect the strength of USC's interdisciplinary research environment. The research projects bring together researchers across different fields to collaborate on foundational research that is especially relevant to USC's diverse, surrounding communities.
"This exceptional work exemplifies what USC Norris Comprehensive Cancer Center does best - bringing together scientists across disciplines to tackle the cancer risk factors that matter most to the communities we serve," said Caryn Lerman, PhD, Director, USC Norris Comprehensive Cancer Center and Associate Dean for Cancer Programs. "Understanding how everyday environmental exposures like PFAS contribute to cancer risk requires exactly this kind of team science, spanning epidemiology, molecular biology, and environmental health."
About this research
The preliminary data supporting these grants were made possible through the NIEHS P30 Southern California Environmental Health Sciences Center and the USC Center for Translational Exposomics Research.
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