Synthetic ‘Forever Chemical’ found widely in environment linked to liver cancer

Exposure to a widely distributed synthetic PFAS chemical in the environment is linked to the most common type of liver cancer.

Keck School of Medicine Founded in 1880, the University of Southern California is one of the world's leading private research universities. It is located in the heart of Los Angeles.

" data-gt-translate-attributes="[{" attribute="">USC scientists find that a common synthetic polyfluoroalkyl substance (PFAS) may increase the risk of liver cancer.

New research links exposure to a synthetic chemical widely found in the environment to nonviral hepatocellular carcinoma, the most common type of liver cancer. Scientists from USC’s Keck School of Medicine conducted the study, which was published August 8, 2022 in the journal JHEP reports.

The chemical, called perfluorooctane sulfate or PFOS, is part 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 referred to as permanent chemicals because they break down very slowly and accumulate in the environment and human tissues, including the liver.

Previous animal research has indicated that exposure to PFAS 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 goes even further,” said Jesse Goodrich, PhD, postdoctoral researcher in the Department of Population Sciences and Public Health at the Keck School of Medicine. “Liver cancer is one of the most serious endpoints of liver disease and this is the first human study to show that PFAS are associated with this disease.”

Higher exposure, higher risk

Human samples collected as part of a large epidemiological study were used by the research team at the Keck School of Medicine. This project, a collaboration between the medical school and the University of Hawaii called the Multiethnic Cohort Study, followed more than 200,000 residents of Los Angeles and Hawaii for the development of cancer and other illnesses.

This large repository of human blood and tissue samples allowed the research team to find 50 participants who eventually developed liver cancer and to evaluate blood samples that were taken before they were diagnosed with cancer. They were also able to compare them to 50 people who did not develop cancer in the same study.

“Part of the reason there have been few human studies is because you need the right samples,” said Veronica Wendy Setiawan, PhD, professor of population science and public health at Keck. School of Medicine. “When you’re looking at environmental exposure, you need samples long before a diagnosis because it takes time for cancer to grow.”

Scientists found several types of PFAS in blood samples taken before the participant developed liver cancer. Research found that the strongest association was between PFOS and liver cancer. It also showed that subjects in the 10% most exposed to PFOS were 4.5 times more likely to develop liver cancer than those with the lowest blood levels of PFOS.

The chemical disrupts normal liver function

The research team was also able to shed light on possible ways in which PFOS impairs normal liver function. Their evaluation of the samples found evidence that PFOS appears to alter the normal process of metabolism of glucose, bile acid metabolism and metabolism of a type of amino acid called a branched chain


Amino acids are a set of organic compounds used to build proteins. There are about 500 naturally occurring known amino acids, though only 20 appear in the genetic code. Proteins consist of one or more chains of amino acids called polypeptides. The sequence of the amino acid chain causes the polypeptide to fold into a shape that is biologically active. The amino acid sequences of proteins are encoded in the genes. Nine proteinogenic amino acids are called "essential" for humans because they cannot be produced from other compounds by the human body and so must be taken in as food.
" data-gt-translate-attributes="[{" attribute="">amino acids in the liver.

Disruption of normal metabolic processes in the liver can lead to 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 of particular concern because people with NAFLD have a much higher risk of developing liver cancer. NAFLD is expected to affect 30% of all adults in the United States by 2030.

Improve knowledge on the health effects of exposure to PFAS

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. have been found in the blood of the general population, leading to a growing awareness of potential health risks.

Some manufacturers have phased out the use of PFOA and PFOS. However, because they are long-lasting, PFAS are found in drinking water, many food products, and the blood of more than 98% of adults in the United States.

Keck School of Medicine researchers, led by Leda Chatzi, MD, PhD, professor of population science and public health, have conducted much of the research on the links between PFAS exposure and injury liver diseases, liver disease and now liver cancer. They hope to further validate their findings about the liver cancer link in a larger study later this year.

“We believe our work provides important insights into the long-term effects of these chemicals on human health, particularly regarding how they can damage normal liver function,” Chatzi said. “This study fills an important gap in our understanding of the true consequences of exposure to these chemicals.”

Reference: “Exposure to perfluoroalkyl substances and risk of hepatocellular carcinoma in a multi-ethnic cohort” by Jesse A. Goodrich, Douglas Walker, Xiangping Lin, Hongxu Wang, Tiffany Lim, Rob McConnell, David V. Conti, Lida Chatzi and Veronica Wendy Setiawan, August 8, 2022, JHEP Reports.
DOI: 10.1016/j.jhepr.2022.100550

Other study authors include Hongxu Wang, Tiffany Lim, Rob Scot McConnell, MD, and David V. Conti, PhD, of USC’s Keck School of Medicine; and Douglas Walker, Ph.D. and Xiangping Lin, Ph.D., of the Icahn School of Medicine at Mount Sinai.

The researchers would like to acknowledge the source of funding for this research which was provided by the Southern California Environmental Health Science Center, supported by the National Institutes of Environmental Health Sciences (P30ES007048).

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