Air pollution linked to lung cancer in non-smokers

Air pollution and exposure to certain herbal medicines have been linked to genetic mutations that may drive lung cancer in people who have never smoked.

While lung cancer has long been associated with smoking, global declines in tobacco use have coincided with a growing proportion of cases in never-smokers.

This trend appears to affect women more than men and is particularly common among people of Asian ancestry and in East Asian countries.

New genomic research suggests that air pollution and environmental exposures could be key factors in these cases.

Researchers analysed lung tumours from 871 never-smokers across 28 regions with varying levels of pollution in Africa, Asia, Europe and North America.

The team, from the University of California San Diego and the US National Cancer Institute, used whole-genome sequencing to detect patterns of DNA mutations known as mutational signatures, which can indicate previous environmental exposures.

They combined this data with satellite and ground-level readings of fine particulate matter to estimate individuals’ long-term exposure to pollution.

People living in more polluted areas showed significantly more mutations in their lung tumours, particularly driver mutations – changes in DNA that are directly involved in cancer development.

These individuals had nearly four times the number of mutations typically associated with tobacco exposure and a 76 per cent increase in mutations linked to ageing.

This does not suggest that pollution leaves its own unique mutational signature, but that it increases the total number of mutations, particularly in DNA damage pathways already known to be linked with cancer.

Marcos Díaz-Gay, now a junior group leader at the Spanish National Cancer Research Centre in Madrid, said: “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.”

A dose-response effect was also observed, with higher pollution levels correlating with more tumour mutations. These tumours also had shorter telomeres – the protective ends of chromosomes – a recognised marker of accelerated cellular ageing.

Secondhand smoke, in contrast, showed little genetic effect.

Although tumours in never-smokers exposed to secondhand smoke had slightly more mutations and shorter telomeres, researchers found no specific mutational signatures or driver mutations.

Co-first author Tongwu Zhang isan Earl Stadtman investigator at the US National Cancer Institute.

The researcher said: “If there is a mutagenic effect of secondhand smoke, it may be too weak for our current tools to detect.

“However, its biological effects are still evident in the significant telomere shortening.”

The researchers noted that measuring secondhand smoke exposure presents challenges.

Díaz-Gay said: “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.”

The team also found a mutational signature linked to aristolochic acid, a known carcinogen present in some traditional Chinese herbal medicines.

This signature appeared almost exclusively in lung tumours from never-smokers in Taiwan.

While aristolochic acid has previously been associated with cancers of the bladder, digestive tract, kidneys and liver when ingested, this study is the first to suggest it may also contribute to lung cancer, potentially through inhalation.

Maria Teresa Landi is an epidemiologist at the US National Cancer Institute and co-senior author.

She said: “This raises new concerns about how traditional remedies might unintentionally raise cancer risk.

“It also presents a public health opportunity for cancer prevention – particularly in Asia.”