Lung cancer: Study reveals 3 origins of the disease in non-smokers

Getting lung cancer as a non-smoker may seem unlikely. And yet, 10 to 20% of reported lung cancers affect people who have never smoked.

Recently, three causes of the onset of the disease in non-smokers have been revealed in a study published in the journal Nature Genetics, by a team of researchers from the National Cancer Institute in Bethesda.

What causes lung cancer?

Lung cancer is not the most common cancer, but it is the most deadly. Also known as bronchial cancers, the majority of cases arise from cells in the lining of the bronchi and bronchioles. In 80% to 90% of cases, it occurs in people who smoke. Many studies have already shown how smoking increases the risk of developing lung cancer.

But smoking is not the only risk factor for the disease: exposure to asbestos, but also to air pollution or radon are also factors. And beyond the environmental factor, lung cancer can occur for no apparent reason. This is the subject of the work of researchers at the National Cancer Institute in Bethesda.

The three subtypes: 'Piano,' 'mezzo forte' and 'forte'

By analysing the genomes of 232 cancerous lung tissue samples taken from non-smokers, the scientists were able to identify 3 subtypes of lung cancer that are unique to them. Their first conclusion is that the mutational signature of the cancer is different from those of smokers, or people who are victims of passive smoking.

They are of endogenous origin, i.e. due to an internal cause. This may be related to the natural process of mutation as well as to the oxidative stress that all cells undergo. To identify them, the three subtypes have been named: 'piano,' 'mezzo forte' and 'forte.'

Towards better management?

The first, 'piano,' is the most common. It is characterised by slow growth and the presence of mutated genes such as UAB1 or KRAS, and slow growth. 'Mezzo forte' is characterised by an amplification of certain genes. This means that there is a copy of the gene in question and mutations in the EGFR gene, which codes for the EGF receptor. Unlike the 'piano' subtype, it grows very fast. Finally, the 'forte' subtype has a duplication of the entire genome.

Maria Teresa Landi, principal author of the study and a doctor at the National Cancer Institute in Bethesda, explains:

We are at the beginning of our understanding of how these tumours evolve. This analysis shows that there is heterogeneity, or diversity, in lung cancers in those who have never smoked.

Her work is beneficial and could contribute to more appropriate management of non-smoking patients.