Mutations caused by pollution in lung cancer in non-smokers revealed

This study highlights the importance of controlling air pollution to prevent respiratory diseases. In this case, it shows that air pollution can cause damage to people's genetic material, which could increase the risk of lung cancer in people who have never smoked. Despite this, smoking remains the most important risk factor for developing lung cancer. We must therefore continue to work towards achieving environments free of tobacco and other air pollutants.

The article is of very high quality. It combines molecular information on lung cancer in non-smokers with information on the degree of air pollution in 28 different geographical areas around the world.

It has previously been reported that non-smokers in Asia show an increase in EGFR gene mutations in areas with high air pollution. This study highlights the importance of air pollution as a causative agent of cancer, reinforcing the need to control air pollution to prevent respiratory health problems, in this case due to its role in lung cancer in non-smokers.

[Regarding possible limitations] This study focuses mainly on the role of air pollution in lung cancer in the non-smoking population, but the effect of air pollution on the smoking population may also be relevant, as it could cause synergism, something that has not been explored in this study, and tobacco remains the main (and preventable) risk factor for developing lung cancer today.

The article provides further evidence on the possible carcinogenic mechanism of environmental pollution in lung cancer. An important aspect is that the study was conducted on people who had never smoked, as this eliminates the possible confounding factor of tobacco and some of the carcinogens it contains, which are similar to those found in certain environmental pollutants, such as polycyclic aromatic hydrocarbons.

The results are in line with previous studies. It should be noted that there may not be a single molecular target (none has been found for lung cancer in smokers), but rather several genes and different molecular pathways are likely to be involved. It provides further insight into the need for measures against environmental pollution, the effects of which are likely to be exacerbated in smokers.

[Regarding possible limitations] The article does not mention the second risk factor for lung cancer according to the WHO, which is exposure to radon. Studies carried out, including in Spain, provide important evidence on the effect of radon exposure on the risk of lung cancer in never-smokers. Another limitation is that the occupational exposure of the participants is not fully assessed, which may play a very important role. Finally, the complexity of measuring exposure to environmental pollution (which varies greatly between individuals even residing in the same area) should be highlighted.

The article is of high scientific quality. It is a comprehensive, well-designed study published in the journal Nature, involving the analysis of 871 complete genomes from lung cancer patients who have never smoked (LCINS). The sample is large, international and diverse, providing significant statistical and representative strength. In addition, the methodology used (high-coverage whole-genome sequencing, multivariate analysis and environmental exposure models) is robust and appropriate for the study's objectives.

The study corroborates previous findings on the high prevalence of mutations in the EGFR and TP53 genes in Asian non-smokers, and in the KRAS gene in Europeans and North Americans. It also confirms that tobacco exposure does not explain most cases of LCINS.

The main new findings are:

• The identification of new mutational signatures, such as SBS40a, which is predominant in LCINS but of unknown aetiology.
• It demonstrates for the first time the association between air pollution (PM2.5) and a significant increase in somatic mutations, shorter telomeres and specific mutational signatures such as SBS4, SBS5 and ID3.

The main implication is that it reinforces the importance of environmental pollution as a key factor in lung carcinogenesis in non-smokers. The work may influence public policies on air pollution control.