Keck College of Medication USC Scientists have discovered that a common man-made polyfluoroalkyl substance (PFAS) may increase the risk of liver cancer.
New research links exposure to a widely found synthetic chemical in the environment with non-viral hepatocellular carcinoma, the most common type of liver cancer. Scientists at USC’s Keck School of Medicine conducted the study, which was published on August 8, 2022 in the journal JHEP Report,
The chemical, called perfluoctane sulfate or PFOS, is one of a class of man-made chemicals known as per- and polyfluoroalkyl substances, or PFAS. Used in a wide range of consumer and industrial products, these chemicals are sometimes called perpetual chemicals because they break down very slowly and accumulate in the environment and human tissue, including the liver.
Earlier research in animals has indicated that PFAS exposure increases the risk of liver cancer. However, this is the first study to confirm an association using human samples.
“It builds on existing research, but takes it a step further,” said Jesse Goodrich, a postdoctoral scholar in the Department of Population and Public Health Sciences at the Keck School of Medicine. “Liver cancer is one of the most serious end points in liver disease and this is the first study in humans to show that PFAS is associated with this disease.”
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Human samples collected as part of a larger epidemiological study were used by the Keck School of Medicine research team. This project, a collaboration between the medical school and the University of Hawaii, called the Multiethnic Cohort Study, has followed more than 200,000 residents of Los Angeles and Hawaii to develop cancer and other diseases.
This large stockpile of human blood and tissue samples allowed the research team to find 50 participants who eventually developed liver cancer and evaluate blood samples taken prior to their cancer diagnosis. They were also able to compare these with 50 people who did not develop cancer from the same study.
“The reason there have been few human studies is because you need the right samples,” said Veronica Wendy Setiawan, a professor of population and public health sciences at the Keck School of Medicine. “When you’re looking at an environmental exposure, you need samples well before diagnosis because cancer takes time to develop.”
The scientists discovered several types of PFAS in blood samples that were taken before the participant developed liver cancer. The research showed that there was the strongest association between PFOS and liver cancer. It also showed that subjects with the top 10% risk of PFOS were 4.5 times more likely to develop liver cancer than those with the lowest levels of PFOS in their blood.
Chemical disrupts normal liver function
The team of researchers was also able to shed light on possible ways in which PFOS altered the normal function of the liver. Their evaluation of the samples found evidence that PFOS alters the normal process of glucose metabolism, bile acid Metabolism, and the metabolism of a type of amino acid called a branched chain amino acids in the liver.
Disruption of normal metabolic processes in the liver can lead to excess fat accumulation in the liver. This is a condition known as non-alcoholic fatty liver disease, or NAFLD. There has been a dramatic and unexplained increase in NAFLD worldwide in recent years. This is particularly worrisome because people with NAFLD have a very high risk of developing liver cancer. NAFLD is expected to affect 30% of all adults in the US by 2030.
Improving knowledge of the health effects of PFAS exposure
PFAS, which are used in a wide range of consumer and industrial products, were first detected in the blood of people exposed to these chemicals in the workplace in the 1970s. By the 1990s, they were found in the blood of the general population, raising awareness of potential health risks.
Some manufacturers have phased out the use of PFOA and PFOS. However, because they are long-lasting, PFAS are in the drinking water, many food products, and blood of more than 98% of adults in the US.
Researchers at the Keck School of Medicine, led by M.D., PhD, professor of population and public health sciences, have conducted much of the research on the relationship between PFAS exposure and liver damage, liver disease, and now liver cancer. They hope to further validate their findings on the link with liver cancer in a larger study later this year.
“We believe our work is providing important insights into the long-term health effects that these chemicals have on human health, particularly with regard to how they can harm normal liver function,” Chatzi said. “This study fills an important gap in our understanding of the true consequences of exposure to these chemicals.”
References: Jesse A. Goodrich, Douglas Walker, Jiangping Lin, Hongxu Wang, Tiffany Lim, Rob McConnell, David V. “Perfluoroalkyl substances and the risk of exposure to hepatocellular carcinoma in a multiracial group” by Conti, Lydia Chatzi and Veronica Wendy Setiawan. 8 August 2022, JHEP Report,
Additional authors of the study include Hongxu Wang, Tiffany Lim, Rob Scott McConnell, MD, and David V., from USC’s Keck School of Medicine. Conti, PhD; and Douglas Walker, PhD, and Jiangping Lin, PhD, from the Icahn School of Medicine at Mount Sinai.
The researchers would like to acknowledge the source of funding for this research was provided by the Southern California Environmental Health Sciences Center, supported by the National Institute of Environmental Health Sciences (P30ES007048).