Metabolite-based biomarkers can predict a patient’s risk of lung cancer by measuring air pollution exposure, according to new research. Signs of heightened risk were detectable several years before participants were diagnosed with the disease. The study adds evidence about how air pollution causes lung cancer and could lead to earlier diagnosis for non-smokers.
The team’s report appeared this week in Nature Communications. Co-senior author Donghai Liang, PhD, commented on the study’s scope. They used high-resolution, untargeted metabolomics to measure more than 1,100 metabolites in over 1,000 pre-diagnostic blood samples. Liang is an associate professor of environmental health at Emory’s Rollins School of Public Health.
Air pollution exposure is already widely recognized as a key environmental cause of lung cancer. However, less is known about air pollution’s biological effects, or which particulates are most harmful. Evidence has accumulated over several decades from large epidemiologic studies conducted around the world.
“A particularly important body of evidence came from prospective cohort studies showing that long-term exposure to particulate matter was associated with lung cancer, including among people who had never smoked,” said Liang.
He added that a major milestone came in 2013. The International Agency for Research on Cancer reviewed more than 1,000 studies from multiple continents. It classified outdoor air pollution as a Group 1 human carcinogen and concluded there was sufficient evidence it causes lung cancer.
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Biological Disruptions Detected in Blood
Researchers analyzed blood samples from 1,357 cancer-free people in the ACS Cancer Prevention Study cohorts. The team found changes in metabolites linked to higher long-term air pollution exposure. These disruptions involved inflammation, oxidative stress, detoxification, and energy metabolism, which are all associated with increased lung cancer risk.
Lung cancer is the leading cause of cancer death in the U.S. The National Cancer Institute currently estimates 661,853 Americans are living with or have a history of the disease. Regular screenings are currently only recommended for adults aged 50-80 years old with a substantial history of tobacco smoking.
“Outdoor air pollution is classified as a human carcinogen, and in epidemiologic studies the association with lung cancer is often strongest among people who have never smoked,” said Ying Wang, PhD. She is a senior principal scientist of epidemiology research at the ACS and a co-senior author of the study.
“That tells us something meaningful is happening biologically, but we still don’t understand the mechanisms,” Wang said. “Studies like this one, which look at what is measurably changing in the body years before a diagnosis, are how we begin to close that gap.”
While clinical application remains years away, these findings suggest a shift in how we approach preventative health. If specific biological signatures can be isolated reliably, public health strategies might eventually expand beyond lifestyle factors to include environmental monitoring for individuals. This could reframe the conversation about who qualifies as “high-risk.”
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Current Screening Guidelines Miss Non-Smokers
“Understanding non-smoking related risk factors, such as air pollution, is important for cancer prevention and early detection,” Liang said. “But the fact that these environmental risk factors are not even considered in current lung cancer screening recommendations highlight that there’s still so much unknown about how air pollution contributes to lung cancer.”
“What is especially exciting about this study is that we now identified measurable changes in human blood metabolome associated with air pollution exposure years before lung cancer was diagnosed,” Liang added. “These new findings give us a clearer picture of the biological processes connecting air pollution and lung cancer.”
Technical Hurdles and Future Testing
More studies will be needed to establish that there is actually a cause and effect relationship between certain pollutants and lung cancer. Liang pointed out their study sample contained a mostly white population. These markers need to be studied in other populations as well.
The analytical platform uses liquid chromatography coupled with tandem mass spectrometry—a sophisticated laboratory-based technology rather than something that would be performed as a point-of-care test in a doctor’s office. This complexity means immediate clinical use isn’t feasible.
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