From the Journals

Pervasive ‘forever chemical’ linked to liver cancer


 

FROM JHEP REPORTS

People exposed to high levels of perfluorooctane sulfonic acid (PFOS) – a widely used synthetic chemical – run an increased risk of hepatocellular carcinoma, researchers say.

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, a postdoctoral scholar in environmental medicine at the University of Southern California, Los Angeles.

“If you’re at risk for liver cancer because you have other risk factors, then these chemicals have the potential to kind of send you over the edge,” he told this news organization.

Dr. Goodrich and colleagues published their research online in JHEP Reports.

Dubbed “forever chemicals” because they can take thousands of years to break down, polyfluoroalkyl substances (PFAS) figure in makeup, food packaging, waterproof clothing, nonstick cookware, firefighting foams, and groundwater. They have spread through the atmosphere into 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,” Dr. Goodrich said.

Previous research has linked PFAS to infertility, pregnancy complications, learning and behavioral problems in children, immune system issues, and higher cholesterol, as well as other cancers. Some experiments in animals suggested PFAS could cause liver cancer, and others showed a correlation between PFAS serum 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 to get really highly exposed groups of people that we started, as scientists, to be able to figure out what was going on,” said Dr. Goodrich.

High exposure, increased incidence

To measure the relationship between PFAS exposure and the incidence of hepatocellular carcinoma more definitively, Dr. Goodrich and colleagues analyzed data from the Multiethnic Cohort Study, a cohort of more than 200,000 people of African, Latin, Native Hawaiian, Japanese, and European ancestry tracked since the early 1990s in California and Hawaii. About 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 blood collection, sex, race, ethnicity, and study area who did not develop the cancer.

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

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

To get some idea of the mechanism by which PFOS might do its damage, the researchers also looked for linkage to levels of metabolites.

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

Similarly, the researchers identified an association among the cancer, PFOS, and alterations in amino acid and glycan biosynthesis pathways.

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