October 2, 2022

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Why do people who never smoke also get lung cancer?

Why do people who never smoke also get lung cancer?



 

Nature Genetics: Why do people who never smoke also get lung cancer?

In modern society, with the increase of average life expectancy, lifestyle changes and the increase of pollutants, the incidence of cancer is also increasing. Among the many types of cancer, lung cancer is undoubtedly one of the most terrifying cancers, and its morbidity and mortality are at the forefront of malignant tumors.

 

According to the latest global cancer burden data released by the World Health Organization’s International Agency for Research on Cancer (IARC) in 2020, there will be 2.2 million new cases of lung cancer worldwide in 2020 (second only to breast cancer) , and 1.8 million new lung cancer deaths (far more than others ). cancer) , it is worth noting that most lung cancer patients have a history of smoking, but 10%-20% of lung cancer patients have never smoked . Also, women who have never smoked are more likely to develop lung cancer and develop the disease earlier than smokers.

 

Environmental risk factors, such as exposure to secondhand smoke, radiation, air pollution, and asbestos, or previous lung disease, may explain some lung cancers in never-smokers, but until now, scientists didn’t know what caused these never-smoking lung cancers The specific cause of the patient’s illness.

 

On September 6, 2021, the National Cancer Institute (NCI) , in conjunction with several research structures, published a research paper entitled: Genomic and evolutionary classification of lung cancer in never smokers in Nature Genetics , a sub-journal of Nature .

 

The study, which analyzed the genomes of non-smoking lung cancer patients, found that most non-smoking lung cancers are caused by genetic mutations that accumulate through natural processes in the body , and is the first to describe three molecular subtypes of lung cancer in never-smokers— — ” piano “, ” mezzo-forte ” and ” forte ” . These insights will help unravel the mysteries of lung cancer in people with no smoking history and may guide the development of more precise clinical treatments.

 

Why do people who never smoke also get lung cancer?

 

 

In this large epidemiological study, researchers performed whole-genome sequencing of 232 never-smokers with lung cancer , mostly of European descent , and compared genetic differences between their tumor and normal tissues to describe Genomic changes in tumor tissue.

 

The tumor types of these lung cancer patients included 189 adenocarcinomas (the most common type of lung cancer) , 36 squamous cell carcinomas, and 7 other tumors of various types. The patients had not received cancer treatment at the time of the study.

 

Why do people who never smoke also get lung cancer?
Whole-genome sequencing analysis of never-smokers with lung cancer

 

 

Next, the researchers combed through the mutational signatures of the tumor genomes of lung cancer patients who had never smoked.

Mutational signatures are mutational patterns associated with specific mutational processes, such as damage caused by the body’s natural activities (such as DNA repair defects or oxidative stress) or by exposure to carcinogens.

Mutational signatures are like archives of tumor activity, leading to the accumulation of mutations that provide clues to cancer development.

 

They found that the majority of tumor genomes in never-smokers had mutational signatures associated with damage to endogenous processes , the natural processes that occur in the body .

 

As expected, because the study was limited to people who never smoked, the researchers did not find any mutational signatures previously associated with direct tobacco exposure.

In addition, they did not find these characteristics in the 62 patients exposed to secondhand smoke.

However, given the small sample size of the studies and the wide variation in the degree of exposure, further research is needed to confirm this.

 

Why do people who never smoke also get lung cancer?Lung cancer in never-smokers is caused by genetic mutations that accumulate through natural processes in the body

 

 

Not only that, but the genomic analysis revealed three new molecular subtypes of lung cancer in never-smokers, which the researchers named based on the level of changes in the tumor’s genome.

 

The ” piano ” (musical term: weak) subtype has the fewest mutations and appears to be involved in stem cell activation, tumors in this subtype grow very slowly, often take many years, and are difficult to treat because it can have many different driver mutation.

 

The ” mezzo-forte ” (music term: medium-strong) subtype has specific chromosomal changes as well as mutations in the growth factor receptor gene EGFR, which is a common type of mutation in lung cancer and shows faster tumor growth.

 

The ” forte ” (musical term: strong) subtype exhibited genome-wide doubling, a genomic change often seen in lung cancers in smokers, and tumors in this subtype also grew rapidly.

 

Why do people who never smoke also get lung cancer?Genomic analysis reveals three molecular subtypes of lung cancer in never-smokers

 

 

Epidemiologist Maria Teresa Landi , Ph.D., corresponding author of the study, said: “What we are seeing is that there are different subtypes of lung cancer in never-smokers with different molecular characteristics and evolutionary processes. In the future, we will It may be possible to have different treatments based on these subtypes .”

 

More importantly, this research finding will guide the development of lung cancer prevention and treatment methods for never-smokers.

For example, the slow-growing piano subtype could provide clinicians with a window of opportunity to detect these tumors early, which are not easily treatable.

In contrast, the rapidly developing mezzo-forte and forte subtypes have only a few major driver mutations, suggesting that these tumors can be identified by a single biopsy and could benefit from targeted therapy.

 


Prevention and targeted therapy based on the molecular characteristics of these subtypes

 

 

Dr. Maria Teresa Landi said that future research directions are to expand the study sample to include people of different ethnic backgrounds and geographic locations, and to have a good description of their history of exposure to lung cancer risk factors. “We are just beginning to understand how these tumors evolve, and our analysis shows that there is heterogeneity and diversity in lung cancer in people who have never smoked, ” he said .

 

 

 

 

 

 

 

 

 

 

 

Reference:
https://www.nature.com/articles/s41588-021-00920-0

Why do people who never smoke also get lung cancer?

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