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Most people who develop lung cancer have a history of smoking. However, in up to a quarter of cases, the patient never turned on in his life.
A new large-scale study on these so-called never smokers has now identified three unique subtypes of lung cancer that appear to occur without an apparent environmental trigger, such as smoke, asbestos, or air pollution. .
“What we are finding is that there are different subtypes of lung cancer in non-smokers that have distinct molecular characteristics and evolutionary processes,” says epidemiologist Maria Teresa Landi of the National Institute of Health. the United States.
“In the future, we may be able to have different treatments based on these subtypes.”
Today, smoking has caused a worldwide epidemic of lung cancer – with 2 million diagnoses occurring each year – but it is still unclear how the disease occurs in those who have never smoked.
The new research has now provided several clues to the origin of these cancers in non-smokers.
When scientists sequenced the genomes of frozen tumor tissue, taken from 232 never-smokers diagnosed with non-small cell lung cancer (by far the most common of the two main types of lung cancer), they noticed several mutational signatures that were not apparent in normal. Lung tissue.
These genetic changes are slightly different from what happens when tobacco smoke causes cancer, suggesting that another form of lung damage could be to blame, potentially something happening in the person’s body, such as faulty DNA repair or oxidative stress.
Even the 62 who had never smoked who had been exposed to second-hand smoke had similar signatures to those who had never smoked in their tumor tissue. This indicates that their illness is the product of internal bodily changes and not environmental stressors, although the sample size in this case is relatively small.
“We need a larger sample with detailed exposure information to really study the impact of second-hand smoke on the development of lung cancer in non-smokers,” Landi admits.
The patients in this study were also mostly of European descent, meaning that future research will need to improve the diversity of its participants.
That said, the authors identified three new lung cancer subtypes in their cohort.
The first and most common subtype they named piano (from the Italian musical term for “gentle and calm”), because it has the fewest genomic mutations. This subtype of lung cancer is associated with progenitor cells, which help create new cells in the lung. It also grows slowly, which means it can be detected up to ten years in advance.
The second subtype is not so easily detected and grows very quickly. He’s been nominated half-strong because its genomic mutations are slightly “stronger” and stronger. This type of lung cancer appears to be linked to mutations in the growth factor receptor gene known as EGFR.
The last subtype of lung cancer in non-smokers is called strong, the “noisiest” of the lot. It has a mutation known as whole genome doubling, which is also seen in lung cancer in smokers.
Even still, its genomic signatures do not strongly match tobacco smokers, even when the patients had experienced secondhand smoke.
“We are starting to understand how these tumors evolve,” says Landi. “This analysis shows that there is heterogeneity, or diversity, in lung cancer in non-smokers.”
Knowing how natural lung cancers arise and how they differ from smoking-induced cancers is crucial if we are to treat them properly. Scientists are already testing treatments that target mutations in the EGFR gene, and one day these could prove effective for people with the disease. half-strong natural lung cancer subtype.
The piano the subtype, on the other hand, will likely be a bit more difficult to treat, as its genetic mutations appear to have multiple factors, making them harder to target with drugs.
Even still, the authors note that if we can find a drug that disrupts signals to progenitor cells in the lungs, it could help stop the growth of piano tumors.
The authors hope their research will continue to inspire research into drugs for lung cancer in the future, especially for those who have never smoked a cigarette in their lives.
The study was published in Genetics of nature.
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