One in four cases of lung cancer affects people who have never smoked, and it is not known why. Now, a study based on genetic mutations in tumors from non-smokers around the world reveals that the polluted air we breathe may be the cause.

Although previous studies had shown an epidemiological relationship between air pollution and lung cancer in non-smokers, the new research shows for the first time that pollution damages DNA and that there is a genetic link between the air we breathe and lung cancer.

The study, published in Nature, was led by Ludmil Alexandrov of the University of California, San Diego (United States) and Maria Teresa Landi of the National Cancer Institute (NCI) in the United States, and includes the participation of scientists Pilar Gallego and Marcos Díaz-Gay from the Spanish National Cancer Research Center (CNIO).

In recent years, cases of lung cancer in people who have never smoked have been increasing. This type of cancer particularly affects Asian women and tends to be more common in East Asia than in Western countries.

"We're seeing this concerning trend that people who have never smoked are increasingly developing lung cancer, and we don't understand why," says Ludmil Alexandrov.

"This is an urgent and growing global problem," adds Landi, an epidemiologist in NCI's Division of Cancer Epidemiology and Genetics.

Until now, most previous studies of lung cancer don't differentiate between data from smokers and nonsmokers, and that "has limited the identification of risk factors in these patients. Our study compiled data from nonsmokers around the world and used genomics to track what exposures might be causing these cancers," she notes.

For the study, the team analyzed lung tumors from 871 people who had never smoked and lived in 28 regions across Africa, Asia,Europe and North America with varying levels of air pollution.

By sequencing the entire genome, they identified distinct patterns of DNA mutations - known as mutational signatures - which are molecular fingerprints of past environmental exposures.

By combining genomic data with estimates of air pollution, they discovered that those who lived in more polluted environments accumulated a significantly higher number of mutations in their lung tumors: They had 3.9 times more mutations related to smoking and 76% more mutations related to aging.

In fact, the study found that the more exposed a person was to pollution, not only did they have more mutations in their cancer, but they also had shorter telomeres - the caps that protect the ends of chromosomes - which is a sign of cellular aging.

"In this study, we saw that the more pollution, the greater the number of mutations, which does not mean that all mutations will cause cancer, but some Yes, they may be related to the carcinogenic process. And the more mutations there are, the more likely it is that one will be bad and cancer will develop," Marcos Díaz Gay, head of the new Digital Genomics Group at CNIO and first signatory of the work, explains to EFE.

In any case, "cancer is not just about mutations; there are other immunological processes that also play a role, but our study supports the hypothesis that mutations associated with pollution could be an important risk factor," he emphasizes.

The study has identified another environmental risk: aristolochic acid, a carcinogen present in certain traditional medicinal herbs, which is responsible for a mutational signature that was found mainly in patients in Taiwan who had never smoked.

Although this acid has previously been linked to bladder, gastrointestinal, kidney, and liver cancers through ingestion, this is the first time it has been linked to lung cancer.

Furthermore, the group identified a new mutational signature of unknown origin, which is found in a higher proportion in lung cancers in non-smokers than in smokers. The signature does not correlate with air pollution, or any other known environmental exposure.

"We observed it in most of the cases in this study, but we still don't know what causes it. This is something completely different, and opens up a completely new area of ??research," Alexandrov acknowledges.

"This mutational signature is very prevalent: In non-smokers it is present in 75% of cases, while in smokers it is only in 27%, but, although at present we cannot determine where it comes from,It is the one that generates the most mutations in non-smokers," Marcos Díaz tells EFE.

In future studies, researchers will include cases of lung cancer in non-smokers from Latin America, the Middle East, and other regions of Africa.

Furthermore, "we want to continue this research by opening new avenues to analyze other potential risks such as marijuana use or vaping, and environmental risks such as radon gas, which we know is a risk factor for lung cancer that is not well known today," he concludes.

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