09/08/2021 6:01 AM
Clarín.com
Good Life
Updated 09/08/2021 7:57 AM
Most people who develop lung cancer have a history of smoking.
However,
between 10% and 20%
of those who suffer from it have never smoked a cigarette, and its causes are not entirely clear.
Hence the importance of a new international study led by researchers from the United States National Cancer Institute (NCI), which sheds light on this issue.
Genomic analysis found that most tumors in
people without a smoking history
are caused by the "accumulation of mutations" caused by natural processes in the body, and describes for the first time three molecular subtypes of lung cancer in people who never smoked. .
"What we are seeing is that there are
different subtypes of
lung
cancer
in which they have never smoked, with different molecular characteristics and evolutionary processes," says epidemiologist Maria Teresa Landi, of the Branch of Integrative Epidemiology of Tumors in the NCI Division.
,
who led the study.
"In the future, it is possible that we may have
different treatments
based on these subtypes," he added about the results of the study, carried out in collaboration with researchers from the National Institute of Environmental Health Sciences, also part of the National Institutes of Health. (NIH) and other institutions, and published in
Nature Genetics.
An uncertain cause
Lung cancer is the
leading cause of
cancer-related
death
worldwide.
Each year, more than 2 million people around the world are diagnosed with the disease.
In people who never smoked, lung cancer occurs more often in women and at a younger age than lung cancer than in smokers.
The
environmental risk factors
, such as exposure to smoke snuff second -
hand, radon gas, pollution of air and asbestos, or had disease previous lung, may explain some lung cancers among those who have never smoked, but Scientists do not yet know what causes most of these cancers.
A wide-ranging study
What the researchers did in this
large epidemiological study
was use whole genome sequencing to characterize genomic changes in tumor tissue and normal tissue from 232 nonsmokers who had been diagnosed with non-small cell lung cancer.
Most tumors in non-smokers are caused by "accumulation of mutations" in the body.
Photo Shutterstock.
The tumors included 189 adenocarcinomas (the most common type of lung cancer), 36 carcinoids, and seven other tumors of various types.
The patients had not yet undergone treatment for their cancer.
Tumor genomes were examined for
mutational signatures
, which are patterns of mutations associated with specific processes and act as the archive of a tumor's activities that led to the accumulation of mutations, thus providing clues to the causes of cancer development.
There is currently a catalog of known mutational signatures, although some have no known cause.
In this study, the researchers found that most of the tumor genomes of those who never smoked had mutational signatures associated with damage from
endogenous processes -
that is, natural processes that occur within the body.
Unsurprisingly, because the study was limited to
those who had never smoked,
the researchers did not find any mutational signatures previously associated with direct exposure to smoking.
Nor did they find such signatures among the 62 patients who had been exposed to secondhand tobacco smoke.
The three types of tumors
Genomic analyzes also revealed
three new subtypes
of lung cancer in those who had never smoked, which the researchers assigned musical names based on the level of "noise" (that is, the number of genomic changes) in the tumors.
The predominant
"piano"
subtype
had the fewest mutations;
appeared to be associated with the activation of progenitor cells that participate in the creation of new cells.
This tumor subtype grows very slowly, over many years, and is difficult to treat because it can have many different driver mutations.
The
"mezzo-forte"
subtype
had specific chromosomal changes, as well as mutations in the EGFR growth factor receptor gene, which is commonly disrupted in lung cancer and showed faster tumor growth.
The researchers found three tumor subtypes in non-smokers.
Illustrative photo Shutterstock.
The
"strong"
subtype
exhibited a complete genome duplication, a genomic change often seen in lung cancers in smokers.
This tumor subtype also grows rapidly.
"We are beginning to distinguish subtypes that could potentially have
different approaches
to prevention and treatment," says Landi.
For example, the slow-growing piano subtype could provide clinicians a window of opportunity to detect these tumors earlier, when they are less difficult to treat.
In contrast, the mezzo-forte and forte subtypes have only a few important driver mutations, suggesting that they could be identified by
a single biopsy
and could benefit from targeted treatments, he said.
A hopeful horizon?
A future direction of this research will be to study
people of different ethnic origins
and geographic locations, and whose history of exposure to lung cancer risk factors is well described.
"We are beginning to understand how these tumors evolve," says Landi.
"This analysis shows that there is heterogeneity or diversity in lung cancers in those who have never smoked," he adds,
"We hope this research
opens new avenues of discovery
for multiple types of cancer," added Stephen J. Chanock, director of the NCI Division of Cancer Epidemiology and Genetics.
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