Ubiquitous ‘Forever Chemical’ linked to liver cancer

People exposed to high levels of perfluorooctane sulfonic acid (PFOS) – a widely used synthetic chemical – are at increased risk of hepatocellular carcinomasay the researchers.

The correlation does not prove that PFOS causes this cancer, and more research is needed, but in the meantime people should limit their exposure to it and others in its class, said Jesse Goodrich, PhD, postdoctoral researcher in environmental medicine at the University of Southern California at Los Angeles.

“If you’re at risk for liver cancer because you have other risk factors, then these chemicals have the potential to send you overboard,” he said. Medscape Medical News.

Goodrich and his colleagues published their research online this month JHEP reports.

Nicknamed “eternal chemicals” because they can take thousands of years to break down, polyfluoroalkyl substances (PFAS) are found in makeup, food packaging, waterproof clothing, non-stick cookware, non-stick foams. fire and groundwater. They spread through the atmosphere as rain and can be found in the blood of most Americans. PFOS is one of the most widely used PFAS.

“You can’t really escape them,” Goodrich said.

Previous research has linked PFAS to infertility, pregnancy complications, learning and behavior problems in children, immune system problems and high cholesterol, as well as other cancers. Some animal experiments have suggested that PFAS can cause liver cancer, and others have shown a correlation between serum PFAS levels and biomarkers associated with liver cancer. But many of these health effects take a long time to develop.

“It wasn’t until we started having very exposed groups of people that we started as scientists so we could figure out what was going on,” Goodrich said.

High exposure, increased incidence

To more precisely measure the relationship between PFAS exposure and the incidence of hepatocellular carcinoma, Goodrich and colleagues analyzed data from the Multiethnic Cohort Study, a cohort of more than 200,000 people of African, Latino, , Hawaiian, Japanese and European followed since the early 1990s in California and Hawaii. Approximately 67,000 participants provided blood samples from 2001 to 2007.

From this cohort, the researchers found 50 people who later developed hepatocellular carcinoma. The researchers matched these patients with 50 controls of similar age at the time of blood collection, gender, race, ethnicity and study area who did not develop cancer.

They found that people with more than 54.9 μg/L of PFOS in their blood before any diagnosis of hepatocellular carcinoma were almost five times more likely to get cancer (odds ratio [OR] 4.5; 95% CI, 1.2 – 16.0), which was statistically significant (P = .02).

This level of PFOS corresponds to the 90th percentile found in the US National Health and Nutrition Examination Survey (NHANES).

To get an idea of ​​the mechanism by which PFOS might cause its damage, the researchers also looked for a link to metabolite levels.

They found an overlap between high levels of PFOS, hepatocellular carcinoma, and high levels of glucose, butyric acid (a short-chain fatty acid), α-ketoisovaleric acid (a branched-chain α-keto acid ) and 7α-hydroxy-3-oxo-4-cholestenoate (a bile acid). These metabolites have been associated in previous studies with metabolic disorders and liver disease.

Similarly, researchers have identified an association between cancer, PFOS, and alterations in amino acid and glycan biosynthetic pathways.

Risk mitigation

The half-life of PFAS in the human body is about 3 to 7 years, Goodrich said.

“There’s not much you can do once they’re in there,” he said. “So the focus has to be on preventing exposure in the first place.”

People can limit exposure by avoiding PFAS-contaminated water or by filtering it, Goodrich said. He recommended avoiding fish from contaminated waterways and non-stick cookware. The Environmental Protection Agency has more detailed recommendations.

But giving patients personalized recommendations is difficult, said Vincent Chen, MD, MS, clinical instructor in gastroenterology at the University of Michigan at Ann Arbor, who was not involved in the study. Most clinicians do not know their patients’ PFOS levels.

“It’s not that easy to pass a test,” Chen said. Medscape Medical News.

People can also mitigate their risk factors for hepatocellular carcinoma, such as poor diet, lack of exercise and smoking, Goodrich said.

The researchers found that patients with hepatocellular carcinoma were more likely to be overweight and to have diabetes, and that PFOS was associated with higher fasting glucose levels. This raises the possibility that PFOS increases the risk of hepatocellular carcinoma by causing diabetes and obesity.

Goodrich and colleagues attempted to answer this question by adjusting for baseline body mass index (BMI) and the diagnosis of diabetes in their statistical analysis.

After adjusting for BMI, they found that the association between PFOS and hepatocellular carcinoma decreased to threefold risk (OR, 2.90; 95% CI, 0.78 – 10.00) and was no longer statistically significant (P = .11).

In contrast, adjusting for diabetes did not change the significance of the relationship between PFOS and cancer (OR, 5.7; 95% CI, 1.10 – 30.00; P = 0.04).

The sample size was likely too small to disentangle this relationship well, Chen said. Still, he says, “I thought it was a very, very important study.”

Levels of PFOS found in the blood of Americans have been declining since the 1999-2000 NHANES, Chen pointed out. But that’s not as reassuring as it sounds.

“The problem is that if you put in a regulation limiting the use of a PFAS, what people can do is just replace it with another PFAS or another molecule, which, as far as we know, could be just as harmful,” Chen said.

Funding was provided by the Southern California Environmental Health Science Center supported by the National Institutes of Health. Goodrich and Chen report no relevant financial relationship.

JHEP Reports. Published online. August 8, 2022. Full Text

Laird Harrison writes about science, health and culture. His work has appeared in national magazines, newspapers, public radio and websites. He is working on a novel about alternate realities in physics. Harrison teaches writing at Writers Grotto. Visit him at www.lairdharrison.com or follow him on Twitter: @LairdH

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