Blood metabolomic changes linked to air pollution appear years before lung cancer diagnosis

Researchers from the American Cancer Society and Emory University's Rollins School of Public Health analyzed blood samples collected from participants in the ACS Cancer Prevention Study cohorts. All 1,357 individuals were free of cancer at the time of blood draw.

The team measured long-term exposure to ambient air pollution for each participant and profiled small molecules, known as metabolites, in the stored blood samples. They identified metabolomic signatures associated with higher pollution exposure that involved pathways related to inflammation, oxidative stress, detoxification, and energy metabolism.

Critically, these blood changes were detectable several years before a subset of participants went on to develop lung cancer. The study, published in Nature Communications, provides molecular-level evidence linking air pollution exposure to biological alterations that precede clinical disease.

Lung cancer remains the leading cause of cancer death in the United States. Current screening guidelines recommend low-dose CT scans only for adults aged 50 to 80 with a substantial smoking history, leaving many at-risk individuals — including never-smokers — without a systematic early-detection pathway.

Outdoor air pollution is classified as a human carcinogen, and epidemiologic studies show its association with lung cancer is often strongest among never-smokers. The newly identified metabolomic signatures offer a potential biological bridge between exposure and disease onset.

Co-senior author Ying Wang, Ph.D., of the American Cancer Society, said studies examining measurable changes years before diagnosis are essential to understanding the mechanisms. Co-senior author Donghai Liang, Ph.D., of Emory University, noted the findings could eventually help identify people at elevated risk and inform whether air pollution exposure should factor into future screening strategies.

The authors emphasize that further validation in independent populations is needed before any clinical application. The research represents a step toward blood-based biomarkers that could expand early detection beyond smoking history alone.