A strong connection has been found between air pollution and lung cancer in non-smokers.

Oncologists around the world are facing a phenomenon they weren't prepared for. Anti-smoking laws are having an effect, especially in developed countries; people are smoking less, and lung cancer cases among smokers are falling. In return, an increasing number of people are developing this tumor without ever having smoked. This tumor affects women more often, and globally it now accounts for up to one in four cases. It is now the fifth most deadly cancer .

This Wednesday, the first study on how air pollution may be one of the main causes of these tumors was published. The study reveals that people with lung cancer who do not smoke exhibit "mutational signatures" and DNA damage very similar to those suffered by those who smoke. The study, published in Nature , also reveals other genetic damage related to premature aging at the cellular level. The results show a strong connection between air pollution and lung cancer without any involvement of tobacco.

Every year, more than four million people die from air pollution. Up to one in four may die from lung cancer. The new study focused on particles 2.5 microns in diameter, produced by the combustion of fossil fuels, which can penetrate deep into the respiratory tract and enter the bloodstream. Ninety-nine percent of the world's population breathes levels of these particles that exceed recommended limits, according to the World Health Organization. In the European Union alone, this type of pollution causes more than 200,000 deaths each year. In 2023, an epidemiological study of 30,000 patients estimated that it only takes three years of breathing polluted air for the incidence of lung cancer in nonsmokers to skyrocket.

The new study takes this study a step further by analyzing the complete genome of 871 nonsmokers with lung cancer in 28 countries—including Spain—and across four continents (Europe, America, Asia, and Africa). The study compared the genetic map of these patients with the levels of fine particle pollution measured in 2.5 microns recorded by both satellites and ground-based measurement stations, thus obtaining an average of pollution exposure in each country.

The results show that higher levels of pollution increase the mutation burden, especially those that promote tumor growth. Patients from more polluted areas have almost four times more mutational signatures related to tobacco, and 76% more of another signature related to premature cellular aging associated with the shortening of telomeres , the shields that protect the chromosomes that group the genome.

"A mutational signature is the imprint that a specific process leaves on our genome," summarizes Pilar Gallego, a biologist at the Spanish National Cancer Research Centre ( CNIO ) and co-author of the study. Each patient can have several of these signatures, the scientist explains. In some cases, the signatures are very similar between smokers and non-smokers, and in others, they are specific to the former, including one that had not been discovered to date and whose causes are unclear, she adds.

“Thanks to this study, we are closer to demonstrating that pollution causes lung cancer, because for the first time we are moving from epidemiological data to examining the effect of pollutants on the genome,” explains CNIO bioinformatician Marcos Díaz-Gay, first author of the paper. The study was coordinated by the United States National Cancer Center and also involved research groups from Canada, China, Turkey, and the United Kingdom, including Charles Swanton 's group, responsible for the work that uncovered the first study exploring how pollution causes cancer in 2023. The paper is also co-authored by Ludmil Alexandrov , a bioinformatician at the University of California, San Diego, who coined the concept of mutational signature and was Díaz-Gay's professor before coming to Spain to lead his own group at the CNIO.

The Spanish team specializes in using artificial intelligence to scan the genome for possible factors that explain certain diseases. This year, the team found a connection between a bacterial toxin in children and the growth of colon cancer in increasingly younger people.

In this new study, the team has revealed another possible risk factor for lung cancer in nonsmokers: the consumption of aristolochic acid . This compound is present in herbs widely used in traditional Chinese medicine. Until now, it had been linked to tumors of the bladder, intestines, stomach, kidney, and liver. The study reveals a genetic signature associated with this compound, which is highly present in nonsmoking patients with lung cancer in Taiwan.

The team now wants to explore their findings on lung cancer and other factors such as marijuana use, e-cigarettes , and exposure to radon, a gas associated with granite that also increases the risk of lung cancer.

"This is an unprecedented study on lung cancer in non-smokers," emphasizes Rosario García-Campelo, a board member of the Spanish Society of Medical Oncology. "It's the largest and most diverse group of patients whose genomic data have ever been analyzed. Although the study cannot conclude that pollution causes these tumors, it does open up many working hypotheses in an area of ​​increasing concern ," she adds.