Lung cancer cases among non-smokers are increasing worldwide — and a new genome study suggests that air pollution may play a significant role in driving this troubling trend.
Researchers from the University of California San Diego (UCSD) and the US National Cancer Institute (NCI) have discovered strong associations between outdoor air pollution and DNA mutations commonly seen in lung cancer, both in smokers and non-smokers. Their findings, published this week, offer some of the clearest evidence yet that smog and soot could contribute to lung cancer risk.
“We’re seeing this problematic trend that never-smokers are increasingly getting lung cancer, but we haven’t understood why,” said Ludmil Alexandrov, a biomolecular scientist at UCSD. “Our research shows that air pollution is strongly associated with the same types of DNA mutations we typically associate with smoking.”
Air pollution linked to key cancer mutations
The study analyzed lung cancer genomes from 871 people across four continents, all of whom had never smoked and had not yet received treatment. Those living in areas with high levels of air pollution were much more likely to have genetic damage in their tumors, including TP53 and EGFR mutations — hallmarks of lung cancers in smokers — as well as shorter telomeres, which are linked to aging.
Non-smokers living in more polluted regions were nearly four times as likely to show the SBS4 mutational signature, which is also strongly associated with cigarette smoking.
Interestingly, the study also found that secondhand smoke exposure showed only a weak link to mutations in non-smokers, suggesting that air pollution may be a more potent driver of genetic damage than previously thought.
“If there is a mutagenic effect of secondhand smoke, it may be too weak for our current tools to detect,” explained Tongwu Zhang, a geneticist at the NCI.
A new mystery signature in non-smokers
While 5% of tumors in non-smokers bore the smoking-related SBS4 signature, a surprising 28% of tumors displayed a previously unknown mutational pattern, dubbed SBS40a, which was not observed in smokers. The cause of SBS40a remains a mystery.
“We see it in a majority of cases in this study, but we don’t yet know what’s driving it,” Alexandrov said. “This is something entirely different, and it opens up a whole new area of investigation.”
Why this research matters
Non-smokers now make up an estimated 10–20% of lung cancer cases in the U.S., a figure that is rising globally. While previous studies have suggested that breathing polluted air might be equivalent to smoking a pack of cigarettes a day, those findings were largely observational.
This new research digs deeper by comparing the actual molecular mechanisms of tumors from non-smokers and smokers, adding weight to the argument that fine particulate matter from air pollution can damage lung tissue and promote cancer in much the same way as tobacco smoke.
Still, the researchers caution that their findings are based on regional air quality data, not on exact measurements of individual exposure.
“This is an urgent and growing global problem that we are working to understand regarding never-smokers,” said Maria Teresa Landi, an NCI epidemiologist.
The team now plans to expand the study with a larger, more diverse global cohort to uncover more about the SBS40a signature and the exact role air pollution plays in lung cancer among non-smokers.