Study Explains Why Most Smokers Never Get to Develop Lung Cancer

Newly published research has uncovered why most smokers don’t develop lung cancer even after years or even decades of consuming tobacco. Even though tobacco is one of the main causes of lung cancer, containing various chemicals that can trigger the disease by damaging DNA, only a small number of smokers actually develop the deadly condition. According to researchers, some cigarette smokers seem to possess certain defense systems that prevent them from developing lung cancer even as they continue to expose themselves to tobacco. 

Conducted by Albert Einstein College of Medicine researchers and published in the journal Nature Genetics, the study sheds light on why lung cancer seemingly affects only a small portion of the over a billion people who smoke tobacco. Even though tobacco contains some of the most well-known carcinogens, the majority of all smokers will remain lung cancer-free. The recent study posits that this may be due to protective mechanisms that keep the deadly condition from emerging. 

Taking advantage of these mechanisms could help researchers determine new means of early lung cancer detection or prevention. The scientists began by studying how DNA mutations typically build up in bronchial basal cells and other healthy cells in the lungs and trigger tumor growth. A high-precision procedure was used to create error-free scans of different cells, enabling the researchers to map mutation patterns in real time accurately in both tumor and healthy cells. 

With access to precise and highly detailed maps of mutation patterns, researchers could study lung cells collected from non-smokers and smokers and compare their mutation loads. This has also allowed them to sequence cells from a wide range of ages and helped them gain more insight into how cancer risk is affected by smoking and age. 

Using a new sequencing method with improved accuracy and error minimization called SCMDA, the researchers looked at lung cells from 14 non-smokers (ages 11–86) and 19 smokers (ages 44–81). 

After comparing mutation accumulations in bronchial epithelial cells, the researchers found that the older smokers had much higher rates of mutations compared to the young non-smokers, suggesting that mutations like small insertions/deletions and single-nucleotide variants build up with age. 

Their findings supported the theory that smoking tobacco speeds up the accumulation of mutations and ultimately raises an individual’s risk of developing cancer. Co-senior study author and pulmonologist Simon Spivack, M.D. notes that subjects who smoked the most tobacco didn’t have the highest mutation levels, suggesting that their bodies may have found a way to resist tobacco-induced DNA damage after around 23 pack-years. 

The research team posits that this may be due to a biological limit that prevents further mutation accumulation past a certain threshold. Once this threshold is reached, Dr. Spivack says defenses such as detoxification mechanisms and DNA repair systems may kick in. These natural defenses could offer valuable insights for researchers working on strategies to prevent lung cancer. They might also help develop better tools for detecting the disease at an earlier, more treatable stage. 

For those smokers that go on to develop lung cancer, it is critical that effective treatment is available to help them battle this disease. As more companies join the likes of Calidi Biotherapeutics Inc. (NYSE American: CLDI) in the search for the next generation of lung cancer treatments, clinicians could have a number of options suited to the needs of different patients. 

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