Researchers at the Keck School of Medicine of USC and USC Norris Comprehensive Cancer Center have secured $7.5m in National Institutes of Health (NIH) funding to investigate whether exposure to per- and polyfluoroalkyl substances (PFAS) contributes to liver cancer and endometrial cancer.
The two five-year R01 grants will support studies examining the relationship between exposure to the synthetic chemicals and cancer development. The endometrial cancer project, awarded $4.1m in June 2026, is expected to be the largest prospective study so far to investigate whether PFAS exposure is associated with the disease.
Researchers will combine long-term health data and blood samples collected before cancer diagnoses with laboratory experiments. The aim is to determine whether PFAS exposure is linked to cancer risk and identify the biological mechanisms that could explain any association.
Investigating PFAS before cancer develops
PFAS are a large group of synthetic chemicals used in products including nonstick cookware, stain-resistant textiles and food packaging. Their resistance to degradation means they can persist in the environment and accumulate in the body.
The chemicals have been detected in the blood of almost all US residents and in around half of public drinking water systems across the country.
Previous research has associated PFAS exposure with several health concerns, including liver damage, kidney disease and some cancers, although the mechanisms behind many of these potential effects remain unclear.
The new research is designed to address that gap by examining exposure before disease develops rather than relying solely on measurements taken after diagnosis.
A closer look at endometrial cancer risk
Endometrial cancer is the most common gynaecological cancer in the US, and incidence has increased over the past decade. Cases are also being diagnosed at younger ages, making potential environmental contributors an important area of investigation.
For the study, researchers will examine pre-diagnostic blood samples from 600 women who subsequently developed endometrial cancer and compare them with samples from 1,200 matched controls who did not develop the disease.
Samples will come from two major prospective studies, the Multiethnic Cohort Study, which has followed participants in Southern California and Hawaii for more than 25 years, and the Southern Community Cohort Study, which includes participants from the southeastern US.
The researchers will assess PFAS concentrations alongside factors such as neighbourhood characteristics, income and access to food. This could help determine whether environmental and socioeconomic conditions influence the relationship between PFAS exposure and endometrial cancer.
One area of interest is food access. People living in food deserts may have fewer options for fresh food and could rely more heavily on packaged or fast food, potentially creating different patterns of exposure to PFAS.
PFAS exposure under investigation in liver cancer
The research programme also includes a separate investigation into hepatocellular carcinoma (HCC), the most common form of liver cancer. That study received $3.4m in NIH funding in March 2026.
Researchers are examining the possibility that PFAS could contribute to the changing causes of liver cancer. While hepatitis B and C infections historically accounted for many cases, improvements in vaccination and antiviral treatment have reduced their contribution.
At the same time, liver cancer associated with metabolic conditions such as obesity and fatty liver disease has increased.
Laboratory evidence suggests that some PFAS can promote fat accumulation in liver cells and trigger cellular changes associated with cancer. The team will investigate these mechanisms using human liver spheroids, three-dimensional laboratory models created from donor cells.
The models will be exposed to different PFAS at varying concentrations and combinations intended to reflect real-world exposure patterns. These experiments will be combined with epidemiological analysis of the long-running Multiethnic Cohort Study.
What the studies could reveal
Together, the projects are intended to move beyond identifying whether PFAS exposure and cancer occur together and investigate how an association might arise.
Because the endometrial cancer research uses blood samples collected before diagnosis, researchers can assess PFAS exposure before the disease develops. This prospective design can help reduce some of the biases associated with measuring exposure after cancer has already been diagnosed.
The researchers ultimately hope the findings will clarify the role of environmental exposures in cancer development and provide evidence that could inform efforts to reduce PFAS exposure and, potentially, cancer risk.
