Whole-Genome Sequencing Study Reveals Air Pollution to Cause More Cancer-Related Changes than Secondhand Smoke

Strategic Insights -

A groundbreaking study has found that fine-particulate air pollution is strongly associated with increased genomic changes in lung cancer tumors among people who have never smoked. By analyzing lung tumors from 871 never-smoker patients across 28 geographic locations worldwide, researchers have linked air pollution exposure to increased cancer-driving and cancer-promoting genetic mutations. This study sheds new light on the mechanisms of lung cancer development in people who have never used tobacco and could lead to more prevention strategies for never-smokers.

Key Takeaways:

  • The study, led by researchers at the National Institutes of Health (NIH) and the University of California, San Diego, found associations between air pollution exposure and changes in the TP53 gene, and other genetic mutational signatures previously associated with tobacco smoking.
  • Researchers analyzed lung tumors from 871 never-smoker patients across 28 geographic locations worldwide as part of the Sherlock-Lung study.
  • The study found that exposure to secondhand smoke was associated with slightly higher mutation burdens and shorter telomeres, but did not lead to an increase in cancer-driving mutations or mutational signatures.
  • The research suggests that secondhand smoke may have a lower overall ability to cause genetic mutations, known as mutagenicity, compared to air pollution.
  • The study was led by researchers at NIH's National Cancer Institute and the University of California, San Diego, and was published in the journal Nature.

Statistics:

  • 871: The number of never-smoker patients from whom lung tumors were analyzed in the study.
  • 28: The number of geographic locations worldwide from which lung tumor samples were collected.
  • 25%: The percentage of all lung cancer cases globally that are attributed to people who have never smoked.
  • 7.2 million: The estimated number of people who die annually worldwide from lung cancer.
  • 5-10: The percentage of lung cancers in never-smokers that are attributed to environmental factors, such as air pollution.

Sources:

  • DÈ¡az-Gay, M and Zhang T et al. The mutagenic forces shaping the genomic landscape of lung cancer in never smokers. Nature. 2025. https://www.nature.com/articles/s41586-025-09219-0
  • National Cancer Institute (NCI) Fact Sheet: Lung Cancer.
  • National Institute of Environmental Health Sciences (NIEHS): Lung Cancer and Air Pollution.