Pollution can cause lung cancer, DNA analysis confirms

One in four cases of lung cancer occurs in people who have never smoked, but until now the cause was unknown. A new international study suggests that air pollution could be behind these cases, revealing for the first time a direct link between exposure to polluted air and genetic mutations in lung tumors in nonsmokers.

Although previous studies have already indicated a link between air pollution and lung cancer in nonsmokers, this new research shows that exposure to polluted air can directly damage DNA, generating genomic fingerprints that explain the origin of certain tumors.

Published in the journal Nature , the study was led by Ludmil Alexandrov (University of California, San Diego) and Maria Teresa Landi (National Cancer Institute, US), with the participation of researchers from the Spanish National Cancer Research Centre (CNIO), including Pilar Gallego and Marcos Díaz-Gay.

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In recent years, lung cancer cases in people who have never smoked have increased significantly, especially among Asian women. This form of cancer is more common in East Asia than in Western countries.

"We're seeing an alarming trend: more and more people who have never smoked are developing lung cancer, and we don't know why," explains Alexandrov. "It's a growing global public health problem," adds Landi, an NCI epidemiology expert.

One of the study's major contributions is that, unlike previous research, it focused exclusively on nonsmokers. "Most previous studies do not separate data between smokers and nonsmokers, which has made it difficult to identify specific risk factors for this group," the team notes.

What did the study do?

The analysis was based on 871 lung tumor samples from nonsmokers living in 28 regions around the world —including Africa, Asia, Europe, and North America—with varying levels of air pollution. By fully sequencing the genome of each tumor, the researchers identified mutational signatures: specific patterns of genetic mutations that function as molecular fingerprints of past environmental exposures.

The results were overwhelming: People living in more polluted areas had a significantly higher number of mutations in their tumors. Specifically, they had 3.9 times more mutations associated with smoking and 76% more mutations associated with aging.

Furthermore, these individuals showed shorter telomeres—structures that protect the ends of chromosomes—which is an indication of accelerated cellular aging. Marcos Díaz-Gay, head of the CNIO Digital Genomics Group and first author of the study, explained:

"Our study shows that the greater the pollution, the more mutations. Not all of them will cause cancer, but the more mutations, the greater the likelihood that a dangerous one will emerge that triggers the disease."

Although cancer is not solely a function of mutations—immunological factors and other cellular processes also play a role— research reinforces the idea that air pollution is a significant risk factor.

An unexpected discovery: mutations caused by traditional herbs

The study also identified an additional environmental source: aristolochic acid, a carcinogen present in some traditional herbal medicines. This substance, already known for its association with kidney, gastrointestinal, and liver cancers, has now also been detected in lung tumors, especially in patients in Taiwan who had never smoked.

Besides, Scientists discovered a completely new mutational signature, more prevalent in tumors of non-smokers than in those of smokers. This signature is not associated with any known environmental sources, including pollution.

"We observe it in most cases of non-smokers, but we still don't know what causes it. It's something completely different and opens up a new field of research," Alexandrov admits.

According to Díaz-Gay, this signature is present in 75% of lung cancer cases in non-smokers, compared to 27% in smokers, and is the one that generates the most mutations in this group.

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The researchers plan to expand their analysis to include lung cancer cases in nonsmokers in Latin America, the Middle East, and other regions of Africa. They also intend to explore other possible risk factors, such as marijuana use, e-cigarette use, and exposure to radon gas, a little-known carcinogen linked to lung cancer.

"Our goal is to continue to delve deeper into the environmental risks that could be behind lung cancer in people who have never smoked, so we can better prevent this disease in the future," Díaz-Gay concludes.

With information from EFE

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