Lung cancer is often simply associated with smoking. Yet nearly one in four lung cancer cases occurs in people who have never smoked. This still poorly understood reality raises many questions, particularly about the role of the environment.
A major international study, published in the prestigious journal Nature and co-authored by Professor Paul Hofman, a member of the RespirERA institute, now sheds new light on the biological mechanisms behind lung cancer in never smokers.
A global analysis of lung cancer in never smokers
As part of the Sherlock-Lung study, researchers analyzed the tumor genomes of 871 patients with lung cancer who had never smoked, from 28 regions around the world. The aim was to identify the “traces” left by different environmental factors in the DNA of cancer cells.
Every form of stress experienced by our cells (air pollution, toxic substances, aging, etc.) can cause specific mutations. These mutations act as biological fingerprints, known as mutational signatures, which scientists are now able to decode.
Marked differences across world regions
The study highlights major genetic differences depending on geographic area:
- In Europe and North America, certain mutations, particularly in the KRAS gene, are more frequent.
- In East Asia, other mutations, such as those affecting the EGFR or TP53 genes, are more commonly observed.
- In Taiwan, a very specific mutational signature is associated with exposure to a naturally occurring toxic substance, aristolochic acid, found in some medicinal plants.
These findings show that lung cancer in never smokers is not a single, uniform disease, but rather reflects a wide range of environmental exposures.
Air pollution: a key factor highlighted
One of the study’s most important findings concerns air pollution. The researchers show that people living in highly polluted areas exhibit:
- More mutations in key cancer-related genes,
- An overall increase in the number of DNA mutations,
- Shortened telomeres—structures that protect our chromosomes and whose erosion is associated with cellular aging.
The higher the level of air pollution, the more pronounced these effects are, suggesting a direct, dose-dependent link between air pollution and genetic alterations.
By contrast, exposure to second-hand smoke does not appear to be associated with specific mutational signatures in this study, underlining the predominant role of air pollution.
Better understanding to improve prevention
These findings provide valuable insight into how the environment shapes the genomes of lung cancers in never smokers. They open the way to:
- Improved prevention strategies, particularly those linked to air quality,
- Advances in diagnosis and precision medicine,
- Greater awareness of the public health challenges posed by air pollution.
Through this publication, the RespirERA institute reaffirms its commitment to advancing research in respiratory health and to improving our understanding of the causes of lung diseases, for the benefit of patients and the wider population.
Link to the publication: The mutagenic forces shaping the genomes of lung cancer in never smokers.
