'Forever Chemicals' and Liver Cancer: Don't Lose Sleep Just Yet

By Cameron English — Sep 06, 2022
Recent news reports alleged that new research has found a link between "forever chemicals" and liver cancer. This was an exaggeration of the results, to say the very least.
Image by jessebridgewater via Pixabay

If the media tells you a group of chemicals is dangerous, be skeptical. The compounds in question may indeed be harmful, but there's a good chance they're reasonably safe and make our lives better. So-called "forever chemicals" may be the best example. Less hyperbolically known as per- and polyfluoroalkyl substances (PFAS), they are found in a wide variety of products we use every day without incident, everything from carpets to cell phones and pacemakers.

Yet reporters, often enabled by scientists and regulators, can't help but publish hyperbolic news stories about PFAS. Consider this recent example from The New York Post:“Forever chemicals in cookware linked to liver cancer in a first human study.” Context-free headline in place, the newspaper went on:

A new study that examined the correlation between liver cancer and the presence of these chemicals in humans found that people with the highest levels of exposure have 350% greater odds of eventually developing the disease.

The researchers involved should've made a comment that qualifies their results, something like, “Our findings are interesting, but they have to be replicated before we can say anything more conclusive.” Instead, the Post rehashed this quote from the press release that accompanied the study:

We believe our work is providing important insights into the long-term health effects that these chemicals have on human health, especially with respect to how they can damage normal liver function,” said study author Dr. Leda Chatzi. “This study fills an important gap in our understanding of the true consequences of exposure to these chemicals.”

This is a bit of a stretch. Dr. Chazti's study tells us nothing about the long-term effects of PFAS exposure; indeed, its design rendered it incapable of doing so. But that's just the beginning of the trouble with this paper. Let's take a closer look at some of its serious limitations.

What did they find?

The researchers performed a nested case-control study involving 50 patients diagnosed with hepatocellular carcinoma (HCC) and 50 disease-free controls [1]. The data came from the Multiethnic Cohort (MEC) Study; cases and controls were matched by age, sex, race/ethnicity, and study area. The researchers then “examined associations of PFAS exposure, altered metabolic pathways, and risk of non-viral HCC.” Conclusion:

This is the first prospective study to demonstrate that PFAS exposure was associated with risk of HCC. Findings from this proof-of-concept study suggest that PFAS exposure may play an important role in the pathology of HCC.

Problems abound. First up, the study evaluated a variety of compounds, but the results were statistically significant for only one, perfluorooctane sulfonic acid aka PFOS (Table 3). Participants with plasma PFOS levels above 54.9 μg/L had 4.5 times higher odds of developing HCC. But that's an enormous figure, far higher than the 1.4 ug/L observed in the general US population, as our resident toxicologist Susan Goldhaber explained in an email. Incidentally, exposure to this particular chemical has declined by 85 percent since 1999. As time progresses, we're exposed to ever-smaller amounts of the only compound in the study that may have posed a liver-cancer risk.

The other significant issue is that PFAS exposure can change over time, influencing the degree of risk someone faces. Accounting for varying exposure is, therefore, very important. How did the researchers do that? They didn't. “... We were only able to measure PFAS at a single time point,” they noted towards the end of the paper. On a related note, Table 2 shows that cases and controls had very similar plasma concentrations of every class of compounds in question; the numbers for PFOS were identical. The study didn't actually have a control group in this regard.

What do other studies show?

The evidence is limited, but a 2009 study conducted in Denmark sheds some light on the PFOS-liver cancer association. Those researchers followed a cohort of 57,053 people for 13 years; just 67 individuals developed liver cancer. PFOS and PFOA concentrations were measured in a sub-cohort of 772 individuals. Conclusion:

Plasma concentrations of perfluorooctanoate and perfluorooctanesulfonate in the general Danish population appear not to be associated with risk of prostate, bladder, pancreatic, or liver cancer.

The authors of the new paper dismissed these results, arguing that “HCC cases were likely a small portion of the total liver cancer cases.” That's not especially compelling, though. All it means is that there were too few cases of HCC to associate the disease with PFOS exposure.

We also need to consider the known causes of HCC. When we do, we find that hepatitis B and C infections are responsible for the majority of HCC cases globally, followed by nonalcoholic fatty liver disease (NAFLD). My colleague Dr. Chuck Dinerstein pointed out that China, for example, has 600 percent more cases of liver cancer than the US per 100,000. "Approximately 80% of [China's] liver cancer cases were attributed to chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV)," this 2017 study explained. According to a July 2021 paper also based on the Multiethic Cohort Study, race significantly influences how someone develops HCC:

African Americans (AA) (59.5%) and Latinos (40.6%) were more likely to be diagnosed with HCV-related HCC. In Japanese Americans (33.1%), Native Hawaiians (39.1%), and whites (34.8%), NAFLD was the most common etiology.

Oddly enough, obesity and diabetes, both important risk factors for liver cancer, were much more prevalent in the cases enrolled in the present study (see Table 1). The contribution of PFOS exposure to liver cancer risk, if it exists, is very small in light of these variables.

Remember that we still don't know if PFOS exposure causes liver damage. Several mechanisms have been proposed; however, there isn't very good data behind any of them. Until we have better evidence, please don't lose any sleep over your exposure to this or any other "forever" chemical.


[1] See this article for background on the study design.

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