In a groundbreaking study, scientists from the National Institutes of Health (NIH) and the University of California, San Diego, have identified a significant link between fine-particulate air pollution and increased genetic mutations in lung cancer tumors among nonsmokers. The research, published in Nature on July 2, 2025, highlights that air pollution may cause more cancer-related genomic changes than secondhand smoke.
This discovery stems from the largest-ever whole-genome analysis of lung cancer in individuals who have never smoked. By examining lung tumors from 871 nonsmoking patients across 28 geographic locations worldwide, researchers were able to associate air pollution exposure with increased cancer-driving and cancer-promoting genetic mutations. This finding could lead to new prevention strategies for nonsmokers, who account for up to 25% of all lung cancer cases globally.
Unveiling the Mechanisms Behind Lung Cancer in Nonsmokers
The study, part of the Sherlock-Lung project, analyzed genomic changes in lung tumors, revealing associations between air pollution exposure and mutations in the TP53 gene, a gene commonly linked to cancer. Additionally, the study found that air pollution was connected to shorter telomeres, the DNA sections at the ends of chromosomes that naturally shorten with age. Shortened telomeres are associated with cellular aging and replication issues, and the study suggests that air pollution accelerates this shortening process.
Prior research on lung cancer has predominantly focused on tobacco smokers, leaving a gap in understanding the disease’s development in nonsmokers. By uncovering how environmental exposures lead to cancer-causing mutations, this study provides crucial insights into the primary drivers of lung cancer in nonsmokers.
Comparing Air Pollution and Secondhand Smoke
Interestingly, while secondhand smoke exposure was linked to slightly higher mutation burdens and shorter telomeres, it did not result in an increase in cancer-driving mutations or mutational signatures. This suggests that secondhand smoke may have a lower mutagenic potential compared to air pollution.
“The mutagenic forces shaping the genomic landscape of lung cancer in never smokers are more influenced by air pollution than by secondhand smoke,” said Maria Teresa Landi, M.D., Ph.D., senior author of the study.
The research was led by Dr. Landi and Tongwu Zhang, Ph.D., at the NIH’s National Cancer Institute and the University of California, San Diego. Their findings underscore the need for public health strategies to mitigate air pollution exposure as a means to prevent lung cancer in nonsmokers.
Implications for Public Health and Future Research
This study’s results emphasize the importance of addressing air pollution as a public health priority. As urbanization and industrial activities continue to rise, the exposure to fine-particulate pollution is expected to increase, posing a greater risk to global health. Policymakers and health organizations may need to implement stricter air quality regulations and promote cleaner technologies to reduce this risk.
Furthermore, the research opens new avenues for scientific inquiry into the environmental factors contributing to cancer. By understanding the mutational processes triggered by air pollution, scientists can develop targeted interventions and prevention strategies for at-risk populations.
According to the World Health Organization, “Air pollution is one of the leading environmental health risks globally, contributing to millions of deaths each year.”
As the study progresses, researchers aim to explore additional environmental factors and their interactions with genetic predispositions to better understand the complex nature of cancer development in nonsmokers.
Next Steps and Ongoing Research
Moving forward, the NIH and its partners plan to expand their research to include other environmental pollutants and their potential impacts on cancer mutations. The goal is to create a comprehensive understanding of how various environmental exposures contribute to cancer, ultimately leading to more effective prevention and treatment strategies.
For more information about the study or to speak with the researchers, Maria Teresa Landi, M.D., Ph.D., and Tongwu Zhang, Ph.D., are available for comment. The full study can be accessed in the July 2025 issue of Nature.
The National Cancer Institute and the NIH continue to lead efforts in cancer research, focusing on reducing the prevalence of cancer and improving patient outcomes through innovative research and public health initiatives.
