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Press release
Monday, September 6, 2021
A genomic analysis of lung cancer in people without a history of smoking found that the majority of these tumors result from the build-up of mutations caused by natural processes in the body. This study was conducted by an international team led by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and described for the first time three molecular subtypes of lung cancer in people who have never smoked.
This information will help unravel the mystery of how lung cancer occurs in people without a history of smoking and may guide the development of more specific clinical treatments. The results were published on September 6, 2021 in Genetics of nature.
“What we are finding is that there are different subtypes of lung cancer in people who have never smoked that have distinct molecular characteristics and evolutionary processes,” said epidemiologist Maria Teresa Landi, MD, Ph.D., Integrative Tumor Epidemiology Branch, NCI Division. of Cancer Epidemiology and Genetics, who led the study, which was done in collaboration with researchers from the National Institute of Environmental Health Sciences, another part of the NIH and other institutions. “In the future, we may be able to have different treatments based on these subtypes. “
Lung cancer is the leading cause of cancer-related deaths worldwide. Each year, more than 2 million people around the world are diagnosed with the disease. Most people who develop lung cancer have a history of smoking, but 10-20% of people who develop lung cancer have never smoked. Lung cancer in people who have never smoked occurs more frequently in women and at an earlier age than lung cancer in smokers.
Environmental risk factors, such as exposure to second-hand tobacco smoke, radon, air pollution and asbestos, or having had lung disease in the past, may explain some cancers. lung cancer in non-smokers, but scientists still don’t know what causes the majority of these cancers. .
In this large epidemiological study, researchers used whole genome sequencing to characterize genomic changes in tumor tissue and compared normal tissues of 232 never smokers, mostly of European origin, who had been diagnosed with cancer. non-small cell lung. 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 received treatment for their cancer.
Researchers combed tumor genomes for mutational signatures, which are patterns of mutations associated with specific mutational processes, such as damage caused by natural activities in the body (for example, faulty repair of DNA or oxidative stress) or exposure to carcinogens. Mutational signatures act as a archive of tumor activities that led to the accumulation of mutations, providing clues as to what caused the cancer to develop. A catalog of known mutational signatures now exists, although some signatures have no known cause. In this study, the researchers found that the majority of the tumor genomes of non-smokers carried mutational signatures associated with damage caused by endogenous processes, that is, natural processes that occur inside the body. body.
As expected, since the study was limited to people who have never smoked, the researchers found no mutational signatures previously associated with direct exposure to smoking. They also did not find these signatures among the 62 patients who had been exposed to second-hand tobacco smoke. However, Dr Landi cautioned that the sample size was small and the level of exposure highly variable.
“We need a larger sample with detailed exposure information to really study the impact of passive smoking on the development of lung cancer in people who have never smoked,” said Dr Landi.
Genomic analyzes also revealed three new subtypes of lung cancer in non-smokers, to which the researchers assigned musical names based on the level of “noise” (that is, the number of genomic changes ) in tumors. The predominant subtype “piano” had the fewest mutations; it appears to be associated with the activation of progenitor cells, which are involved in the creation of new cells. This tumor subtype grows extremely slowly, over many years, and is difficult to treat because it can have many different motor mutations. The ‘mezzo-forte’ subtype exhibited specific chromosomal changes as well as mutations in the growth factor receptor gene EGFR, which is commonly impaired in lung cancer, and has exhibited faster tumor growth. The strong subtype exhibited whole genome doubling, a genomic change often seen in lung cancer in smokers. This tumor subtype also grows rapidly.
“We are starting to distinguish subtypes that could potentially have different approaches to prevention and treatment,” said Dr Landi. For example, the slow-growing piano subtype might give 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 show only a few major motor mutations, suggesting that these tumors could be identified with a single biopsy and could benefit from targeted treatments, she said.
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 starting to understand how these tumors evolve,” said Dr Landi. This analysis shows that there is heterogeneity, or diversity, in lung cancer in non-smokers.
Stephen J. Chanock, MD, director of NCI’s Division of Cancer Epidemiology and Genetics, said: “We expect this detective-like investigation into the characteristics of genomic tumors to open up new avenues of investigation. discovery for several types of cancer.
The study was conducted by NCI’s intramural research program and the National Institute of Environmental Health Sciences.
About the National Cancer Institute (NCI): The NCI leads the National Cancer Control Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through cancer prevention and biology research, the development of new interventions and the training and mentoring of new researchers. For more information on cancer, please visit the NCI website at cancer.gov or call the NCI contact center, Cancer Information Service, at 1-800-4-CANCER (1-800 -422-6237).
About the National Institutes of Health (NIH):The NIH, the national agency for medical research, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the principal federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.
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