Posted on 09/09/2021 11:44:58 AM PDT by Red Badger
Most people who develop lung cancer have a history of smoking. However, in up to a quarter of all cases, the patient has never lit up in their life.
A large new study on these so-called never smokers has now identified three unique subtypes of lung cancer that seem to arise with no apparent environmental trigger – such as smoke, asbestos, or air pollution.
"What we're seeing is that there are different subtypes of lung cancer in never smokers that have distinct molecular characteristics and evolutionary processes," explains epidemiologist Maria Teresa Landi from the United States' National Institute of Health.
"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 – yet it's still unknown how this disease arises in those who have never smoked at all.
The new research has now provided several clues as to how these non-smoker cancers originate.
When scientists sequenced the genomes of frozen tumor tissue, sampled from 232 never smokers diagnosed with non-small cell lung cancer (by far the more 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 to what occurs when tobacco smoke causes cancer, which suggests an alternative form of lung damage might be to blame, potentially something occurring in the person's body, like faulty DNA repair or oxidative stress.
Even those 62 never smokers who had been exposed to secondhand smoke showed similar signatures to other never smokers in their tumor tissue. This indicates their disease is a product of internal bodily changes and not environmental stressors, although the sample size in this case is relatively small.
"We need a larger sample size with detailed information on exposure to really study the impact of secondhand tobacco smoking on the development of lung cancer in never smokers," admits Landi.
The patients from this study were also mostly of European descent, which means future research will need to improve on the diversity of its participants.
That said, the authors have identified three novel subtypes of lung cancer in their cohort.
The first and most common subtype they have named piano (from the Italian music term for 'soft and quiet'), because it shows 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 really quickly. It has been named mezzo-forte because its genomic mutations are slightly 'louder' and stronger. This type of lung cancer appears to be linked to mutations in the growth factor receptor gene known as EGFR.
The final subtype of non-smoker lung cancer is called forte, the 'loudest' of the lot. It exhibits a mutation known as whole-genome doubling, which is also seen in lung cancers among smokers.
Even still, its genomic signatures do not strongly match tobacco smokers, even when the patients had experienced secondhand smoke.
"We're at the beginning of understanding how these tumors evolve," says Landi. "This analysis shows that there is heterogeneity, or diversity, in lung cancers in never smokers."
Knowing how natural lung cancers arise and how they differ from smoking-induced cancers is crucial if we want to treat them properly. Already, scientists are testing treatments that target mutations in the EGFR gene, and one day, these could prove effective for those with the mezzo-forte subtype of naturally occurring lung cancer.
The piano subtype, on the other hand, will probably be a bit harder to treat, as its genetic mutations seem to have multiple drivers, which makes them harder to target with drugs.
Even still, the authors note that if we can find a pharmaceutical that disrupts signals to the lungs' progenitor cells, it could help halt the growth of piano tumors.
The authors hope their investigations will continue to inspire drug research for lung cancers in the future, especially for those who have never puffed on a cigarette in their life.
The study was published in Nature Genetics.
https://www.nature.com/articles/s41588-021-00920-0
A buncha lawyers aren’t going to be pleased to hear about this. Of course, tobacco company lawyers will.
And will we finally be rid of those mesothelioma commercials that have been playing late nights since the late 50s?
OOPS! They let it slip that "second hand" smoke has nothing to do with it. Expect some corrections or re-edits of this article within 24 hours.
ashkenazi jew might have this issue...they seem to have cancer quirks
Could be many things. Even incense.....................
FU, Rob Reiner!
Guess we will have to wait for Fauci to express an opinion, then we can use that as the "Well, it's not that" conclusion.
My father-in-law is 85 and up until recently smoked heavily all his life. Never got lung cancer....................
There is a poster here who knows several Doctors in Cancer research. Maybe with American Cancer Society. I can’t remember.
She said they think that there is a strong genetic component and gave this illustration which still sticks with me:
You could swim in asbestos and not get cancer if you dont have the genetic weakness.
“father-in-law”
1 out of 6 smokers get lung cancer, so that’s 5 out of 6 that don’t.
For non, it’s 1 out of 60.
I’ve often thought that as well.
The opposite of that is my Mother-in-law’s family.
Cancer has killed all her brothers, 5 of them, but all her sisters, 5 of them, are still alive...........
Even still, the authors note that if we can find a pharmaceutical that disrupts signals to the lungs’ progenitor cells, it could help halt the growth of piano tumors.
And the great thing? You don’t have to test them anymore! Just throw it out there!
I call my cigars “Karen-repellent”.
They think one puff at one hundred feet will strike them dead.
:-)
All cancer represents a loss of cellular energy, the genetic transformation from creating and using energy to creating tissue. Diet and exercise help stave off this transformation. Not everyone with good diet and exercise will avoid cancer, and not everyone with bad diet and exercise will get cancer.
in my mother’s immediate family, her parents and sister died of cancer and no one lived longer than 50 years old. My mother made it to 85, but she finally got cancer herself and passed before Christmas. The cancer she got was extremely rare. Her parents and sister didn’t have a rare cancer as far as we know - parents had colon CA and sister died of lung cancer (she smoked).
“OOPS! They let it slip that “second hand” smoke has nothing to do with it. Expect some corrections or re-edits of this article within 24 hours. “
Yes they did.
I'd like to know where you got that figure. The statistics used to say that 7% of pack a day smokers got lung cancer. That is 7 out of 100.
If they aren’t examining the DNA of Keith Richards and Ozzy Osbourne to figure this out, they should be.
My brother had two dogs die of lung cancer about ten years apart and different breeds.
Wonder if it’s the same cause
“I’d like to know “
Stuck in my head from at least 10 years ago, I can try to look up. Note your stat refers to pack a day. The 1 in 6 refers to all smokers, i.e., including those over a pack a day.
Other number that stuck with me it takes 30 “pack years” (1 pack a day for 30 yrs or 2 for 15, etc.) to present irreversable and noticeable pulmonary reduction in later life compared to non smokers, measured in FEV - forced expiratory volume.
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