The National Institutes of Health awarded two grants totaling $7.5 million to the researchers at the USC Keck School of Medicine and the USC Norris Comprehensive Cancer Center last month.

The purpose of the grant money, according to a Keck press release, is to study whether exposure to per- and polyfluoroalkyl substances increases the risk of liver and endometrial cancer. The studies that the grants are supporting will be the first of their kind, specifically analyzing PFAS as a driver of these cancers.

“PFAS are what we call forever chemicals. We are all exposed to them, and they are extremely resistant,” said Lida Chatzi, director of the USC Superfund Research Program for PFAS Assessment, Remediation and Prevention. “Once they enter the human body, they can affect every single tissue and organ.”

According to the Environmental Protection Agency, PFAS are widely used, long-lasting chemicals that break down slowly in both the environment and human body. These substances are widely used in consumer, commercial and industrial goods, leading to contamination of water, air, fish and soil globally.

Wendy Setiawan, a professor of population and public health sciences and medicine, said the goal of the project is to research an association between PFAS and an increased risk of liver and endometrial cancer. The grant will fund the first rounds of these studies to progress the understanding of how human exposure to PFAS could be associated with cancers in general.

Setiawan described them as a “large family of synthetic chemicals,” useful for resisting heat, water, oil and grease for consumer and industrial applications. Many non-stick products and pans have historically used PFAS.

“There [is] more evidence showing that they are related to adverse health outcomes,” Setiawan said. “They’re called ‘forever chemicals’ because they break down extremely slowly. They can persist in the environment — and also in our bodies — over a long period of time.”

In vitro studies indicate that the exposure of liver cells to PFAS may contribute to the accumulation of fat in the liver, becoming a more significant cause of liver carcinogenesis.

Chatzi said there is a “strong body of evidence” suggesting that exposure to PFAS is associated with steatotic liver disease, which is one of the biggest risk factors for liver cancer. As a silent disease, no symptoms appear in the early stages.

According to Setiawan, researchers plan to expose liver spheroids to different mixtures of PFAS that mimic exposures in the natural environment to observe potential changes in the cells.

“We want to know what type of PFAS is specifically associated with changes in the liver cell,” Setiawan said. “It could be a mixture, because in [the] real world, people get exposed to multiple compounds, not just one.”

Besides liver cancer, endometrial cancer is also one of the cancers experiencing an increasing incidence in the past two decades.

“If you look at other cancers, the incidence may be going down, but [for] endometrial cancer, [it] is going up,” Setiawan said. “Endometrial cancer is also an understudied cancer with very interesting disparities in terms of certain race [and] ethnic groups having higher risks, and we don’t understand why.”

Setiawan said exposure to PFAS could result in a higher risk of contracting endometrial cancer because they “disrupt the balance of hormones in the human body.”

After studying PFAS for the past 15 years, Chatzi’s research has also shown associations with childhood and hormonal outcomes, including childhood obesity and type two diabetes — Mount Sinai reported that PFAs are linked to these higher risks.

Human intake of PFAS comes mainly from contaminated drinking water, but it is identifiable and can be prevented.

“If their water is contaminated with PFAS and if they live close to a site that is actually contaminating the water with PFAS, that’s something that they can easily find out from their water provider because the water provider should disclose this information,” Chatzi said.

Another potential source of PFAS comes from food wrappers from fast food. Fast food establishments use PFAS to make the wrappers oil-resistant.

Setiawan added that firefighters have also been shown to have higher exposure to PFAS due to their protective clothing..

“Certain occupations may be at higher risk of getting exposed to PFAS, but in general, PFAS are pretty widespread in the community,” Setiawan said.

However, potential limitations of the study include restricted sample size and population variety, which could result in a lack of generalizability in the final findings.

“These types of studies are always limited by sample size,” Setiawan said. “Statistically, in order for us to be able to look at interactions between neighborhood factors with their other risk factors, you need a large sample size.”

Additionally, the samples are only collected in Southern California and parts of Hawaii. Therefore, researchers may not be able to generalize their results to people who live outside of those locations.

According to Keck School of Medicine, beginning this research to find a novel risk factor for fatal cancers, such as liver and endometrial cancer, is very promising.

“The two back-to-back awards reflect the strength of USC’s interdisciplinary research environment,” Shen writes., “The research projects bring together researchers across different fields to collaborate on foundational research that is especially relevant to USC’s diverse, surrounding communities.”