Overall, in recent years, around 50,000 new annual cases of bronchopulmonary cancer have been diagnosed in France. In 2020.12.6 % of lung cancers concerned non-smokers, compared to only 7.2 % in 2000 (KBP-2020 study).
In addition to a disturbing progression, “we see that 80 to 90 % of these so-called ‘non-smoking lung cancers arise among women,” said Pr Nicolas Girard, oncologist and pulmonologist at the Institut Curie (Paris).
Why such importance among the female sex? “The specific reasons are poorly understood, but a possible role in hormonal factors is envisaged. »»
A certain type of bronchopulmonary tumors in non-smoking
In people who have never smoked, lung cancers are most often what oncologists call adenocarcinomas, that is to say tumors that preferentially develop in pulmonary alveoli (small structures where gas exchanges are made), rather than epidermoid carcinomas, which appear mainly in bronchi.
In addition, these are in the majority of cases of so -called “non -small cell” cancers (category of most frequent lung cancer), associated with specific genetic mutations.
“Indeed, non-smokers often have particular ‘alterations’ of certain genes, alone capable of transforming a normal cell into a cancer cell, explains Professor Girard. This is particularly the case with the mutation of the EGFR gene (receiver of the epidermal growth factor), the most common: it is found in around 50 % of pulmonary tumors in non-smokers, against less than 10 % in those encountered in smokers. Other alterations have also been identified – about fifteen at this stage – including the ALK mutation, present in almost 20 % of patients, or ROS1, observed in around 15 %. »»
The impact of air pollution is becoming clearer
Air pollution contributes in part to the appearance of lung cancers in non-smokers, as shown by various epidemiological and experimental studies.
“Its role can be attributed to the fine particles present in the air, which, due to their small size (≤ 2.5 microns, PM2.5), are capable of penetrating deep into the pulmonary parenchyma,” says the oncologist. The inhalation of fine particles (PM2.5) would then create an inflammatory microenvironment in the pulmonary parenchyma (the functional fabric of the lungs, editor’s note), promoting the development of lung cancer by stimulating the expression of mutations already present in this healthy fabric, such as spontaneous mutations of the EGFR gene. »»
A French study of 2024 from this famous KBP-2020 cohort cited above, analyzed this link. For each city of residence of the 9,000 patients with bronchopulmonary cancer, a level of exposure to the main pollutants (fine particles PM2.5 and PM10, ozone, nitrogen dioxide and radon) has been calculated.
The results show in particular that people living in highly polluted areas have an increased risk of 50 % of developing lung cancer with EGFR mutation which is a mutation much more often encountered in cancers of the non-smoking lung.
This level of risk is comparable to that of passive smoking (but still remains 15 times lower than that of active smoking).
Identification of mutational signatures favored by pollution
The Sherlock-Lung study (University of California-San Diego and National Cancer Institute) published last July in Nature confirms the impact of pollution, from pulmonary tumors of 871 patients who have never smoked, from 28 sites in the world.
They highlighted a strong link between on the one hand exposure to air pollution and, on the other hand, the increase in certain key changes in DNA promoting the development of cancer in non-smokers (EGFR, KRAS …) but also of mutagenic signatures (kinds of molecular footprints of past exhibitions) such as SBS4, SBS5 …, in particular those related to aging and cancer development.
“Pollution increases the total number of mutations, in particular in the known ways of DNA damage. We note that air pollution is associated with an increase in somatic mutations, including those that correspond to the known mutational signatures attributed to smoking and aging, “comments Marcos Díaz-Gay, the main co-author of the study (Spanish national center for cancer, Madrid).
The researchers also observed a dose-answer relationship: the more a person was exposed to pollution, the more the changes were numerous within the tumor.
The study also shows that air pollution accelerates the shortening of telomeres (DNA segments at the ends of chromosomes).
However, shorter telomeres promote the uncontrolled multiplication of cells and therefore the potential appearance of cancer mutations. Normally, a gene (TP53) stops these cells or triggers their death, but its action becomes ineffective under the effect of mutations linked to a strong exposure to pollution.
Note: Radon, present in the outside environment, and asbestos, are two other risk factors in people who have never smoked.
Sources: KBP-2020 studies (CPLF 2022, and 2024); Díaz-Gay, M., Zhang, T., Hoang, Ph et al. The Mutagenic Forces Shaping the Genomes of Lung Cancer in Never Smokers. Nature 644, 133–144 (2025); Survival of people with cancer in mainland France 1989-2018-Public lung/health France December 2020; Swanton C et al. Lung adenocarcinoma promotion by air pollutants. Nature. 2023 APR; 616 (7955): 159-167; Interview with Pr Girard (2025).
