NIH study links particulate air pollution to increased mutations in lung cancers among nonsmokers

Research news (Nature; July 2, 2025)

Scientists at the NIH/NCI and the University of California, San Diego reported findings from the Sherlock-Lung study, described as the largest whole-genome analysis of lung cancer in never-smokers.

Study dataset: Whole-genome analysis of lung tumors from 871 never-smoker patients across 28 geographic locations worldwide.

Key associations reported:

• Fine-particulate air pollution (including pollution from vehicles and industry) was strongly associated with increased genomic changes in tumors from never-smokers, including cancer-driving and cancer-promoting mutations.
• Air pollution exposure was linked to changes in TP53 and to mutational signatures previously associated with tobacco smoking.
• Air pollution exposure was also associated with shorter telomeres, and investigators reported evidence consistent with premature telomere shortening.

Secondhand smoke comparison: Exposure to secondhand smoke was associated with slightly higher mutation burdens and shorter telomeres versus no exposure, but did not correspond to increased cancer-driving mutations or mutational signatures, suggesting potentially lower mutagenicity than air pollution (as interpreted by the authors).

The authors stated these findings may help clarify mechanisms and drivers of lung cancer in never-smokers, a group estimated to represent up to 25% of lung cancer cases globally.

Reference: Díaz-Gay M, Zhang T, et al. Nature (2025). DOI: 10.1038/s41586-025-09219-0.