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September 06, 2022
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Exposure to widespread synthetic pollutants linked to surprising ‘magnitude’ of HCC risk

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Investigators have identified an elevated risk for hepatocellular carcinoma in people exposed to per- and polyfluoroalkyl substances, according to a study published in JHEP Reports.

“We were surprised by the magnitude of the association between [per- and polyfluoroalkyl substance (PFAS)] levels and risk of liver cancer,” Jesse A. Goodrich, PhD, a post-doctoral scholar in population and public health sciences at the University of Southern California Keck School of Medicine, told Healio. “Based on previous research, we hypothesized that PFAS would slightly increase the risk of cancer. But once we got the data, we were really surprised by the magnitude of the effects we saw.”

“We were surprised by the magnitude of the association between [per- and polyfluoroalkyl substance (PFAS)] levels and risk of liver cancer. Based on previous research, we hypothesized that PFAS would slightly increase the risk of cancer. But once we got the data, we were really surprised by the magnitude of the effects we saw.” – Jesse A. Goodrich, PhD

According to researchers, previous studies in animals suggest exposure to PFAS could increase risk for fatty liver and HCC by affecting hepatic lipid, amino acid and glucose metabolism. With limited data on humans, Goodrich and colleagues analyzed 50 individuals with nonviral HCC and 50 matched controls from the Multiethnic Cohort (MEC) Study, made up of more than 200,000 residents in California and Hawaii, to determine PFAS exposures and risk for HCC.

“PFAS are persistent and ubiquitous chemicals which have been widely used in industry and consumer products for more than 60 years,” Goodrich and colleagues wrote. “In humans, biological half-lives of long-chain PFAS such as perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA) and perfluorohexane sulfonate (PFHxS) range between 3 and 7 years.”

According to study results, people with high PFOS levels (> 55 g/L) had a 4.5-fold increased risk for HCC (OR = 4.5; 95% CI, 1.2-16).

“In addition to looking at whether PFAS exposure was linked to liver cancer, we also looked at whether PFAS exposure was associated with differences in metabolite levels that have previously been shown to increase the risk of liver cancer,” Goodrich said. “This helped us look at the potential mechanisms, such as why PFAS may cause cancer.”

Researchers reported four metabolites linking PFAS exposure with HCC: glucose, butyric acid, alpha-ketoisovaleric acid and 7alpha-hydroxy-3-oxo-4-cholesternoate.

“Previous studies have seen similar findings in different populations, but no previous studies have combined this information to examine whether PFAS cause cancer,” Goodrich said. “This helped add additional evidence to our findings.”

While acknowledging that larger studies are needed to confirm this data, researchers wrote that this proof-of-concept study highlights the role PFAS exposure may play in the development of HCC.

“Our results add to the body of evidence suggesting that clinicians should start offering blood PFAS testing to patients in order to help identify patients at high risk of certain diseases, including liver cancer,” Goodrich said. “The National Academies of Science, Engineering and Medicine recently put out a report recommending clinicians offer blood PFAS level testing to patients. In patients with high levels of PFAS, they recommend screening for dyslipidemia, thyroid function and thyroid cancer, kidney cancer, testicular cancer, and ulcerative colitis.”

He added, “Our findings build on these recent guidelines and potentially suggest that patients with high PFAS levels should also be screened for liver cancer.”

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