Cigarette smoking is the leading cause of lung cancer, yet only a minority of smokers develop the disease. A study conducted by scientists at the Albert Einstein College of Medicine and published online in Nature Genetics suggests that some smokers may have robust mechanisms that protect them from lung cancer by limiting mutations.
Smoking leads to lung cancer by triggering mutations PHOTOShutterstock
The findings could help identify those smokers who face an increased risk of the disease and therefore require particularly close monitoring.
“This could prove to be an important step towards prevention and early diagnosis of the risk of lung cancer“said Simon Spivack, co-senior author of the study, professor of medicine, epidemiology and health.
Overcoming barriers to studying cell mutations
It has long been assumed to smoke leads to lung cancer by triggering DNA mutations in normal lung cells.
“But this could never have been proven until our study because there was no way to precisely quantify mutations in normal cells”said Jan Vijg, PhD, co-author of the study.
Dr Vijg overcame this hurdle several years ago by developing an improved method for whole genome sequencing of single cells.
Single cell whole genome sequencing methods can introduce sequencing errors that are difficult to distinguish from true mutations, a major flaw when analyzing cells containing rare and random mutations.
Dr. Vijg solved this problem by developing a new sequencing technique called single-cell multiple displacement amplification (SCMDA). As reported in Nature Methods in 2017, this method accounts for and reduces sequencing errors.
Einstein’s researchers used SCMDA to compare the mutational landscape of normal lung epithelial cells (the cells that line the lungs) from two types of people: 14 never smokers, ages 11 to 86, and 19 smokers, aged 44 to 81, who smoked a maximum of 116 packs of cigarettes.
Cells were harvested from patients undergoing bronchoscopy for non-cancer diagnostic testing.
“These lung cells survive for years, even decades, and therefore can accumulate mutations with both age and smoking.” said Dr. Spivack. “Of all lung cell types, these are among the most likely to become cancerous.”
Mutations caused by smoking
The researchers found that the mutations (single nucleotide variants and small insertions and deletions) accumulated in the lung cells of non-smokers as they aged, and that many more mutations were found in the lung cells of smokers. “This experimentally confirms that smoking increases the risk of lung cancer by increasing the frequency of mutations, as previously hypothesized,” said Dr. Spivack. “This is probably one of the reasons why so few non-smokers get lung cancer, while 10% to 20% of lifelong smokers do.”
Another finding of the study: The number of cellular mutations detected in lung cells increased in a straight line with the number of pack-years smoked – and presumably also increased the risk of lung cancer. But interestingly, the increase in the number of cell mutations stopped after 23 pack-years of exposure.
“Heavy smokers did not have the highest mutational burden,” said Dr. Spivack. “Our data suggest that these individuals may have survived this long despite heavy smoking because they were able to suppress the accumulation of further mutations. This flattening of mutations could result from the fact that these individuals had highly efficient systems for repairing mutations. DNA damage or to detoxify cigarette smoke”.
The discovery led to a new direction of research. “We now want to develop new tests that can measure a person’s ability to repair DNA or detoxify, which could provide a new way to assess lung cancer risk“said Dr. Vijg.
How smoking affects your body
According to the Cleveland Clinic, tobacco use harms every organ in the body. Smoking tobacco introduces not only nicotine into the lungs, blood and organs, but also over 5,000 chemicals, including many carcinogens (chemicals that cause cancer).
The harm caused by smoking can significantly shorten your life. In fact, smoking is the number one preventable cause of death in the United States.
Pregnant women who smoke also put their unborn babies at risk. Possible effects on pregnancy include:
– ectopic pregnancy, a life-threatening condition in which the embryo implants itself outside the uterus;
– spontaneous abortions;
– stillborn;
– congenital malformations, such as cleft palate.
– low birth weight.
What other conditions can be caused or made worse by tobacco
In addition to the known cancer risks, the Cleveland Clinic says smoking causes many other chronic (long-term) health problems that require ongoing care. Specific smoking-related problems that require treatment include:
– lower cholesterol HDL (good) and increased blood pressure (increased risks of heart attack and stroke);
– decreased oxygen supply to the heart and other body tissues (increased risk of coronary heart disease, peripheral arterial disease and diabetes);
– more common routine illnesses, such as colds, especially in children living with smokers;
– poorer lung function (ability to get enough oxygen) leading to COPD, asthma, bronchitis or emphysema.
