Air pollution and herbal medicines could be behind lung cancer in non-smokers, study finds
While smoking is a major risk factor for lung cancer, rates of the malignancy appear to be increasing among those who have never smoked, even with tobacco use declining globally.
Previous studies have shown that lung cancer disproportionately affects non-smoking women, particularly those with Asian ancestry, and is more prevalent in East Asia than in Western nations.
Now, a new study, published on Wednesday in the journal Nature, provides compelling evidence that air pollution and herbal medicines could be behind genetic mutations linked to the development of lung cancer in non-smokers.
'We are seeing this problematic trend that never-smokers are increasingly getting lung cancer, but we haven't understood why,' said Ludmil Alexandrov, an author of the study from the University of California San Diego.
'Our research shows that air pollution is strongly associated with the same types of DNA mutations we typically associate with smoking.'
Most lung cancer prevalence studies haven't separated data of smokers from that of non-smokers, providing limited insights into potential causes in those patients.
The latest study collected data from never-smokers worldwide and used genomics to find environmental factors likely behind these cancers.
'This is an urgent and growing global problem that we are working to understand regarding never-smokers,' said Maria Teresa Landi, co-author of the study from the US National Cancer Institute.
While previous studies have shown a potential link between air pollution and lung cancer in never-smokers, the new research goes further by revealing a genomic link.
In this comprehensive study, scientists analysed lung tumours from 871 never-smokers living in 28 regions with different levels of air pollution across Africa, Asia, Europe and North America.
Researchers used genome sequencing methods to identify distinct patterns of genetic mutations which act like molecular fingerprints of past exposures.
They then compared the genomic data with pollution estimates based on satellite and ground-level measurements of fine particulate matter.
This helped them estimate long-term exposure of the patients to air pollution.
The study found that never-smokers living in more polluted environments had significantly more mutations in their lung tumours, particularly the kinds which directly promote cancer development.
Scientists also found more molecular signatures in this group, which are linked to cancer and serve as a record of all past exposures to mutation-causing environmental factors.
For instance, these individuals had a nearly 4-fold increase in a mutational signature molecule linked to tobacco smoking and a 76 per cent increase in another signature linked to ageing.
'What we see is that air pollution is associated with an increase in somatic mutations, including those that fall under known mutational signatures attributed to tobacco smoking and ageing,' said Marcos Díaz-Gay, co-author of the study.
Scientists found that the more pollution someone was exposed to, the more mutations were found in their lung tumours, as well as greater signs of their cells undergoing accelerated ageing.
Another environmental risk unravelled by the study was aristolochic acid, a known cancer-causing chemical found in some traditional Chinese and Ayurvedic herbal medicines.
This chemical, extracted from plants of the birthwort family, was found linked to a signature mutation in lung tumours of never-smokers from Taiwan.
Although ingestion of this plant chemical has been linked previously to bladder, gut, kidney, and liver cancers, the latest study is the first to report evidence that it may contribute to lung cancer.
'This raises new concerns about how traditional remedies might unintentionally raise cancer risk,' Dr Landi said. 'It also presents a public health opportunity for cancer prevention, particularly in Asia.'
The study also found an intriguing new mutation signature which appears in the lung tumours of most never-smokers but is absent in smokers.
'We don't yet know what's driving it,' Dr Alexandrov said.
'This is something entirely different, and it opens up a whole new area of investigation.'
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