Air Pollution Causes Genetic Mutations Linked to Lung Cancer in Non-Smokers, Major Study Finds

A global genomic study has confirmed that high levels of air pollution are directly associated with DNA mutations that lead to lung cancer in individuals who have never smoked, offering new insight into one of the deadliest cancers worldwide.

Published in Nature and based on findings from the Sherlock-Lung study, the research examined the cancer genomes of 871 people diagnosed with lung cancer who had never used tobacco. These individuals came from 28 locations across Europe, North America, Africa, and Asia. The study reveals that air pollution plays a central role in driving specific genetic mutations previously attributed primarily to smoking, including those in the TP53 gene.

The investigation builds on prior epidemiological research linking environmental exposure to lung cancer. Around 25% of all lung cancer cases globally now occur in people with no history of smoking, a figure that continues to rise in urbanised regions with poor air quality.

Researchers found a strong correlation between elevated air pollution and increased mutational activity within lung tumour genomes. Specifically, individuals living in areas with high pollution levels were significantly more likely to exhibit mutations in TP53—a gene known for its role in tumour suppression and frequently associated with tobacco-related cancers. In these same regions, the team also observed shortened telomeres—DNA structures that protect chromosome ends—which are a marker of accelerated cellular ageing and a recognised risk factor in cancer development.

Professor Ludmil Alexandrov, one of the study’s contributors, stated: “Our analysis shows that air pollution is associated with many of the same mutational signatures typically seen in smokers, reinforcing the idea that polluted environments carry a measurable genetic risk.”

Among the most striking findings was the increased prevalence of the mutational signature known as SBS4, which has historically been linked to tobacco exposure. This signature was found to be nearly four times more common in individuals living in heavily polluted areas. The study also identified a 76% increase in signature SBS5, a ‘clock-like’ mutational process associated with ageing, in patients from high-pollution zones. Both signatures were shown to exhibit a positive dose–response relationship with air pollution: the more polluted the environment, the greater the number of mutations observed.

The data also revealed geographical variation in the types of mutations found. KRAS mutations were significantly more prevalent in adenocarcinomas of never-smokers from North America and Europe compared with those from East Asia. In contrast, EGFR and TP53 mutations were more common in East Asian patients. One additional signature, SBS22a—linked to exposure to aristolochic acid—was observed almost exclusively in patients from Taiwan, indicating regional environmental or medicinal exposures.

Notably, the study found no significant association between exposure to secondhand tobacco smoke and the presence of key driver mutations or overall mutational signatures. In contrast, air pollution demonstrated a consistent and measurable impact on the cancer genome, supporting a direct mutagenic effect.

Lung cancer remains the leading cause of cancer-related mortality globally, with approximately 2.5 million new cases diagnosed each year. Despite advances in treatment, survival rates remain low, particularly when the disease is detected at a late stage. The new evidence presented in this study suggests that prevention strategies must be expanded beyond anti-smoking campaigns to include environmental protection and air quality management.

The research highlights that mutational processes in lung cancer are shaped by a complex interplay of local environmental factors. While urban pollution has long been associated with respiratory illnesses, the present study confirms its role in directly altering the genetic material within lung cells.

The implications for public health policy are considerable. The study’s authors call for revised air quality standards and increased investment in pollution mitigation strategies, particularly in densely populated urban centres. They also recommend that lung cancer risk assessments be updated to include environmental exposure alongside traditional factors such as age, family history, and smoking status.

“Our findings suggest that even people with no history of smoking can develop the same genetic mutations linked to tobacco exposure, solely due to the air they breathe,” said Professor Alexandrov. “This reinforces the urgent need to view air pollution as a direct carcinogen.”

The research adds to mounting scientific consensus that outdoor air pollution—particularly fine particulate matter (PM2.5)—should be treated as a primary risk factor for cancer, on par with tobacco. While emerging therapies offer hope for improved survival, the authors emphasise that preventing exposure remains the most effective means of reducing cancer incidence.

The study represents one of the most comprehensive genomic assessments of lung cancer in non-smokers to date, and underscores the growing role of environmental factors in cancer biology. It provides a critical foundation for future research into the mechanisms through which polluted air drives carcinogenesis, as well as potential biomarkers for early detection in exposed populations.