Pollution Could Cause Lung Cancer in Non-Smokers

Lung cancer in never-smokers appears to be driven by an increase in mutations that have now, for the first time, been linked specifically to air pollution, including fine particulate matter from industrial and vehicle emissions, according to the largest whole-genome analysis of lung cancers ever conducted in never-smokers, involving 871 untreated patients from 28 regions across four continents.

The study, part of the Sherlock-Lung study and published today in Nature , is coordinated by Maria Teresa Landi and colleagues from the US National Institutes of Health (NIH) and the University of California, San Diego. In particular, mutations in the TP53 gene and some mutational signatures (i.e. molecular signs that indicate DNA damage) already known because they are correlated with tobacco smoke are strongly associated with pollution.

How common is lung cancer in non-smokers?

With approximately 2.5 million new diagnoses per year worldwide (over 44 thousand in Italy), lung cancer is one of the most frequent and in approximately 3 out of 4 cases it is caused by cigarette smoking. In fact, it is estimated that 25% of cases occur in non-smokers, with a slight prevalence in women and in those with a family history of lung cancer. There are also differences at a geographical level, with more cases in East Asia and Eastern Europe than in North America and Western Europe.

The study

The patients in this study were 79% women. In terms of tumor type, the majority were adenocarcinomas (84.6%). Information on passive smoking was collected for 458 patients, and approximately half were exposed.

The genes involved

Let's move on to genomic analyses. Scientists first tried to understand which tissues acquire mutations after exposure to air pollution, in order to identify the "driver" mutations, that is, those that "guided" or promoted the development of the tumors analyzed. According to the data, the KRAS gene mutation was almost 4 times more common in tumors of patients from North America and Europe rather than from East Asia, where instead EGFR mutations are prevalent and, as anticipated, TP53.

Pollution shortens telomeres

The researchers also observed a correlation between exposure to pollution and shorter telomere length: telomeres are the final portions of chromosomes that, like caps, protect DNA and “shorten” with each cell replication. Telomeres normally shorten with aging, but in this case pollution also seems to have an impact.

The effect was dose-dependent: people from regions with high levels of pollution were more likely to have mutations in the TP53 gene and shorter telomeres. A particular “genetic signature,” already associated with exposure to aristolochic acid (a known carcinogen), was also observed almost exclusively in patients from Taiwan.

Data on passive smoking

Compared to secondhand smoke, Landi and colleagues observed a slightly higher “load” of mutations and telomere shortening in exposed patients compared to unexposed ones, but the effect was still smaller than that of pollution. In addition, secondhand smoke was not associated with an increase in driver mutations or mutational signatures known to promote cancer.

A gap to fill

Several epidemiological studies have already shown that exposure to environmental factors, including pollution and passive smoking, can increase the risk of lung cancer in non-smokers. However, most genomic research has so far focused mainly on populations of smoking patients. Now, "our results - the researchers write - show the diversity of mutational processes of lung cancer in non-smokers".