The natural ability to protect against cancer-causing mutations is believed to be the reason some long-term smokers do not develop lung cancer.
Smoking is the primary cause of lung cancer, yet only a small number of smokers actually develop the disease.
A new study led by scientists at Albert Einstein College of Medicine in the United States, published in the journal Nature Genetics on April 11, shows that some smokers possess a powerful mechanism that protects them from lung cancer by limiting mutations.
Smoking increases the risk of lung cancer by increasing mutation frequency.
Professor Simon Spivack from Albert Einstein College of Medicine, a co-author of the study, stated: “This could be a significant breakthrough for the prevention and early detection of lung cancer risk, thereby avoiding extreme measures in combating this disease.”
According to Science Daily, it has long been thought that smoking leads to lung cancer by triggering DNA mutations in normal lung cells.
“However, this had never been proven until our study because there was no accurate way to quantify mutations in normal cells,” said Professor Jan Vijg, another co-author of the study.
Methods for whole-genome sequencing of single cells can introduce errors, making it difficult to distinguish real mutations. In their recently published paper, Dr. Vijg’s team addressed this issue by developing a new sequencing technique called single-cell multi-displacement amplification (SCMDA), which minimizes existing errors.
The expert team used SCMDA to compare mutations in normal lung epithelial cells from two groups of individuals: 14 non-smokers (aged 11-86) and 19 smokers (aged 44-81), who had smoked an average of 116 packs of cigarettes per year. The cells were collected from patients undergoing bronchoscopies for non-cancer-related diagnostic tests.
“These lung cells can exist for many years, even decades. Therefore, they can accumulate mutations due to age and smoking. Among all types of lung cells, these are some of the most likely to become cancerous,” Professor Spivack noted.
Researchers found that mutations accumulate in the lung cells of non-smokers as they age, while more mutations were identified in the lung cells of smokers.
This demonstrates that smoking increases the risk of lung cancer by elevating mutation frequency. “This could be a significant reason why so few non-smokers develop lung cancer, while 10-20% of long-term smokers do,” the expert explained.
They also discovered that the number of mutations in lung cells increases proportionally with the number of years of smoking, meaning the risk of lung cancer also rises. However, notably, this increase plateaus after 23 years.
Dr. Spivack remarked: “The heaviest smokers are not necessarily the ones with the highest mutation rates. They may have survived without developing lung cancer due to their body’s ability to prevent the accumulation of mutations. This phenomenon could arise from these individuals having very proficient DNA damage repair or detoxification systems against cigarette smoke.”
This discovery has led to new research directions. Dr. Vijg stated: “We hope to develop new tests that can measure someone’s DNA repair or detoxification capabilities, which could then provide new methods for assessing lung cancer risk.”
