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Air Pollution, DNA Mutations, and Lung Cancer in Never-Smokers 🫁

Air Pollution, DNA Mutations, and Lung Cancer in Never-Smokers Health is our most precious asset.

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Air Pollution, DNA Mutations, and Lung Cancer in Never-Smokers 🫁

Health is our most precious asset.


Lung cancer is often regarded as a disease of smokers, but a surprising number of patients have never smoked today.ucsd.edu. In fact, people without a smoking history now account for roughly 25% of lung cancer cases worldwide dceg.cancer.gov. This trend is especially strong among women and in East Asia today.ucsd.edu. Long-term exposure to fine particulate air pollution (PM₂.₅) is already known to increase lung cancer risk: the World Health Organization’s cancer agency classifies PM₂.₅ as a proven lung carcinogen who.int. These findings have driven scientists to look for genetic clues in tumors of never-smokers, to trace their environmental causes.

Researchers at UC San Diego and the National Cancer Institute (NIH) have led a major new study (published July 2025 in Nature) to decode this mystery. They performed whole-genome sequencing on lung tumors from 871 never-smoker patients living in 28 regions of Africa, Asia, Europe and North America today.ucsd.edu. This allowed them to identify mutational signatures: patterns of DNA damage that act like molecular fingerprints of past exposures today.ucsd.edu. The team then compared these signatures with long-term air pollution levels (from satellite and ground data for PM₂.₅) at each patient’s location.

Key study results:

  • Higher mutation burden: Never-smoker tumors from highly polluted areas had many more DNA changes, including extra driver mutations that directly promote cancer today.ucsd.edu.
  • Smoking-like patterns: These tumors showed a 3.9-fold increase in a mutation signature (called SBS4) normally linked to tobacco smoke today.ucsd.edu dceg.cancer.gov. In other words, polluted air left behind DNA damage similar to what smoking does.
  • Aging signals: There was also a 76% rise in another signature (SBS5) associated with cellular aging today.ucsd.edu dceg.cancer.gov. This suggests pollution accelerates DNA changes tied to getting older.
  • Dose–response effect: The more polluted the environment, the more mutations were found in the tumors, and the shorter the telomeres (chromosome “caps”) in the lung cells today.ucsd.edunih.gov. Short telomeres are a sign of accelerated cellular aging.
  • Tumor-suppressor genes: Key cancer genes were affected. For example, tumors from high-pollution regions often had mutations in TP53 (a major anti-cancer gene) dceg.cancer.gov.

Together, these results offer compelling genomic evidence that air pollution is damaging lung DNA in never-smokers. As Ludmil Alexandrov (UCSD) notes, the tumors from polluted areas carried “the same types of DNA mutations we typically associate with smoking” today.ucsd.edu. In short, fine particulates (like PM₂.₅) seem to cause molecular injury to lung cells, raising cancer risk much as tobacco does. The effect is dose-dependent: higher pollution means more genetic harm today.ucsd.edu.

Other Exposures: Smoke and Herbal Risks

The study also looked at other factors. Interestingly, secondhand smoke left only a weak signature in the DNA. Tumors from never-smokers with secondhand smoke exposure showed a slight increase in mutations and shorter telomeres, but no clear smoking-related mutation pattern or extra driver mutations today.ucsd.edunih.gov. In other words, passive smoke appeared much less mutagenic in this analysis than heavy outdoor pollution.

By contrast, one environmental culprit did stand out: aristolochic acid, a known carcinogen found in some traditional Chinese herbal remedies. A distinct mutation signature (SBS22) linked to aristolochic acid was found almost exclusively in lung cancers of never-smokers from Taiwan today.ucsd.edu dceg.cancer.gov. This is the first time this signature has been seen in lung tumors (it was known in bladder, kidney and liver cancers). It suggests that inhaling or ingesting certain herbal medicines could inadvertently raise lung cancer risk. As NCI epidemiologist Maria Landi points out, this “raises new concerns about how traditional remedies might unintentionally raise cancer risk”today.ucsd.edu.

New Mystery: An Unknown Mutation Signature

The researchers made one more intriguing finding: a new mutation signature, labeled SBS40, appeared in most never-smoker lung tumors but was absent in smokers. Its cause is still unknown today.ucsd.edudceg.cancer.gov. This unexplained genetic pattern suggests there may be another, as-yet-unidentified exposure or biological process driving lung cancer in never-smokers. Discovering what causes SBS40 is an open question for future research.

Protecting Your Health 🏥

These findings highlight the importance of clean air for everyone’s health. Until city air gets cleaner, there are steps you can take to reduce personal risk:

  • Monitor air quality: Use local apps or weather reports to check PM₂.₅ levels each day. When pollution is high, limit prolonged outdoor exercise.
  • Use masks & filters: On smoggy days, wear a well-fitted mask (like an N95) to filter tiny particles cdn.who.int. At home, use air purifiers or keep windows closed on polluted days to improve indoor air cdn.who.int.
  • Healthy lifestyle: Don’t start smoking and avoid secondhand smoke. Eat well and exercise regularly to keep your lungs strong. Get medical check-ups for any persistent cough or breathing issues.

Above all, stay informed and advocate for clean air. Breathing safe, clean air is a shared public-health goal. By understanding these new study results, we are reminded that health is our most precious asset. Reducing pollution exposure through personal choices and public policy, can help protect our lungs and save lives.

Sources: Recent genomic research from UCSD and NCI today.ucsd.edu dceg.cancer.gov, NIH press release nih.govnih.gov, and WHO air-quality guidance who.int cdn.who.int confirm these findings. All facts are drawn from peer-reviewed studies and official reports.

📚 Citations

  1. UC San Diego. (2025, July 2). Air pollution may contribute to development of lung cancer in never-smokers, new study finds. UCSD Today. https://today.ucsd.edu/story/air-pollution-may-contribute-to-development-of-lung-cancer-in-never-smokers-new-study-finds
  2. National Cancer Institute (NCI). (2025, July 2). Air pollution, medicinal herbs linked to lung cancer mutagenesis in never smokers. Division of Cancer Epidemiology and Genetics. https://dceg.cancer.gov/news-events/news/2025/sherlock-air-pollution-lung-cancer
  3. National Institutes of Health (NIH). (2025, July 2). NIH study links particulate air pollution to increased mutations in lung cancers among nonsmokers. https://www.nih.gov/news-events/news-releases/nih-study-links-particulate-air-pollution-increased-mutations-lung-cancers-among-nonsmokers
  4. World Health Organization (WHO). (n.d.). Air quality, energy and health – Health impacts: Types of pollutants. https://www.who.int/teams/environment-climate-change-and-health/air-quality-and-health/health-impacts/types-of-pollutants
  5. World Health Organization (WHO). (n.d.). Advisory for air pollution and health precautions. https://cdn.who.int/media/docs/default-source/searo/india/news-pdf/advisory-for-air-pollution.pdf?sfvrsn=8407dff2_2

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