New research from the Keck School of Medicine at USC reveals that communities with drinking water contaminated by manufactured chemicals called per- and polyfluoroalkyl substances (PFAS) face up to a 33% higher risk of developing certain cancers.

Published in the Journal of Exposure Science and Environmental Epidemiology and funded by the National Institutes of Health, this is the first U.S.-based study to directly examine the link between PFAS contamination in drinking water and cancer.

PFAS are widely used in consumer products like furniture and food packaging and have been detected in approximately 45% of drinking water supplies across the United States. These chemicals are slow to degrade and accumulate in the body over time. Previous studies have connected PFAS exposure to several health issues, including kidney, breast, and testicular cancers.

To paint a more comprehensive picture of PFAS and cancer risk, Keck School of Medicine researchers conducted an ecological study, which uses large population-level datasets to identify patterns of exposure and associated risk. They found that between 2016 and 2021, counties across the U.S. with PFAS-contaminated drinking water had a higher incidence of certain types of cancer, which differed by sex. Overall, PFAS in drinking water are estimated to contribute to more than 6,800 cancer cases each year, based on the most recent data from the U.S. Environmental Protection Agency (EPA).

“These findings allow us to draw an initial conclusion about the link between certain rare cancers and PFAS,” said Shiwen (Sherlock) Li, PhD, a postdoctoral researcher in the Department of Population and Public Health Sciences at the Keck School of Medicine and first author of the study. “This suggests that it’s worth researching each of these links in a more individualized and precise way.”

In addition to providing a roadmap for researchers, the findings underscore the importance of regulating PFAS. Starting in 2029, the EPA will police levels of six types of PFAS in drinking water, but stricter limits may ultimately be needed to protect public health, Li said.

The toll of PFAS

To understand how PFAS contamination relates to cancer incidence, the researchers compared two exhaustive datasets—one covering all reported cancer cases and the other including all data on PFAS in drinking water data across the country. Data on cancer cases between 2016 and 2021 were obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, while data on PFAS levels in public drinking water (2013-2024) came from the EPA’s Unregulated Contaminant Monitoring Rule programs.

Li and his colleagues controlled for a number of factors that could influence cancer risk. At the individual level, these included age and sex; at the county level, they ruled out changes in cancer incidence due to socioeconomic status, smoking rates, obesity prevalence, urbanicity (how urban or rural an area is), and the presence of other pollutants.

The researchers then compared cancer incidence in each county to PFAS contamination in the drinking water, using the EPA’s recommended cutoffs for each type of PFAS. Counties where drinking water surpassed the recommended maximum levels of PFAS had a higher incidence of digestive, endocrine, respiratory, and mouth and throat cancers. Increases in incidence ranged from slightly elevated at 2% to substantially elevated at 33% (the increased incidence of mouth and throat cancers linked to perfluorobutanesulfonic acid, or PFBS).

Males in counties with contaminated drinking water had a higher incidence of leukemia, as well as cancers of the urinary system, brain, and soft tissues, compared to males living in areas with uncontaminated water. Females had a higher incidence of cancers in the thyroid, mouth, and throat, and soft tissues. Based on the latest available EPA data, the researchers estimate that PFAS contamination of drinking water contributes to 6,864 cancer cases per year.

“When people hear that PFAS is associated with cancer, it’s hard to know how it’s relevant. By calculating the number of attributable cancer cases, we’re able to estimate how many people may be affected,” Li said, including inferring the personal and financial toll of these cases year after year.

Protecting public health

These population-level findings reveal associations between PFAS and rare cancers that might otherwise go unnoticed. Next, individual-level studies are needed to determine whether the link is causal and to explore what biological mechanisms are involved.

On the regulation side, the results add to the mounting evidence that PFAS levels should be limited, and suggest that proposed changes may not go far enough.

“Certain PFAS that were less studied need to be monitored more, and regulators need to think about other PFAS that may not be strictly regulated yet,” Li said.