A new study has found strong genetic evidence that air pollution may contribute to the development of lung cancer in people who have never smoked or smoked only minimally.
The research, undertaken by the University of California San Diego and the U.S. National Cancer Institute, aimed to discover why, as global smoking rates have declined, there has been a rise in lung cancer cases among non-smokers.
This form of cancer disproportionately affects women, particularly those of East Asian ancestry, and is more common in East Asian countries than in the West.
Published today in the journal Nature, the research involved analysing lung tumors from 871 non-smokers living in 28 different regions worldwide, in Africa, Asia, Europe and North America.
The researchers used whole-genome sequencing to identify specific DNA mutations which act like fingerprints of environmental exposures such as air pollution.
By comparing these genetic patterns with long-term air pollution data, the researchers found that people living in more polluted environments had significantly more mutations in their lung tumors.
Many of these mutations are known to promote the development of cancer and some resembled the type typically seen in smokers, despite the fact that those involved had little or no history of smoking. This included a nearly fourfold increase in a mutation commonly associated with tobacco exposure and a 76% increase in another linked to aging.
The researchers point out that their findings do not suggest that air pollution causes a completely new or unique type of DNA damage, rather that it increases the overall number of mutations in the DNA of lung cells. These mutations show up in known ‘mutational signatures’ – patterns of DNA damage that scientists have already associated with tobacco smoking, aging or other causes.
Maria Teresa Landi, epidemiologist in the Division of Cancer Epidemiology and Genetics at the NCI and co-senior author of the study, said: ‘This is an urgent and growing global problem that we are working to understand regarding never-smokers.
‘Most previous lung cancer studies have not separated data of smokers from non-smokers, which has limited insights into potential causes in those patients. We have designed a study to collect data from never-smokers around the world and use genomics to trace back what exposures might be causing these cancers.’
The team made two additional findings of interest.
Firstly, they found that exposure to secondhand cigarette smoke did not lead to the same DNA mutation patterns as caused by exposure to air pollution.
However, as co-first author Marcos Díaz-Gay, pointed out: ‘It’s difficult to get that kind of information because it depends on various factors such as amount of time one was exposed; how far one was from exposure; and how often one shared a space with someone else who smoked, for example.”
Secondly, they also found a link between lung cancer and aristolochic acid, a known carcinogen which can be found in traditional Chinese herbal medicines. This mutational signature was found almost exclusively in lung tumors from non-smokers in Taiwan.
While being a known carcinogen, aristolochic acid has not previously been implicated in lung cancer. Researchers suspect that inhalation of herbal remedies may be responsible.
The team also unearthed a new puzzle by indentifying a new mutational signature that appears in the lung cancers of most non-smokers but not in smokers. Its cause remains unknown
Study co-senior author Ludmil Alexandrov, professor of bioengineering and cellular and molecular medicine at UC San Diego explains: ‘We see it in a majority of cases in this study, but we don’t yet know what’s driving it. This is something entirely different, and it opens up a whole new area of investigation.’
The full report can be read here.
Photo: National Cancer Institute
Leave a Reply