Gene mutations in any organism can have several causes. Smoking, however, has been known to increase the risk of around 17 cancers, including lung cancer, bladder cancer, kidney cancer, and many more. Tobacco smoke is a complex mixture of chemicals, at least 60 of which are carcinogens. A new analysis shows that DNA in cancerous tissues of smokers are different from those in cancerous tissues of non-smokers. Cancer geneticist Ludmil Alexandrov and his international research team conducted an experiment in which they analyzed and examined mutational signatures and DNA methylation in DNA extracted from 5000 genome sequences, half of which were from smokers. What showed the increase in cancer risks in smokers were the mutational signatures 2,4,5,13, and 16.
Signature 4 mutation signals damage to guanine and it appears in DNA of cells which were exposed to chemicals from burnt products, such as tar in cigarette smoke. This signature was found in non-smokers' tumors, but less often. Smokers with lung squamous cancer, lung adenocarcinoma and larynx cancers had high numbers of signature 4 mutations, while cancers of oral cavity, pharynx, and esophagus had much less signature 4 mutations. Even though the reason why these tissues didn't have as much signature 4 mutations, despite being the most directly exposed to smoke, is unclear, the team speculates that these tissues might metabolize smoke differently.
Another difference observed between the smoker's damaged DNA and that of non-smokers was the presence of signature 5 mutations. This signature normally shows up in all cancer types but its cause is still unknown. However, it is known that it increases with age and the analysis revealed that the more a person smoked, the more signature 5 mutations were present. Smokers with lung adenocarcinoma also appeared to have more signature 2 and 13 than non-smokers with the same disease. These could have resulted from overactive DNA editing machinery. However they are found in many types cancer and it's still unclear how smoking influenced the increase in these signatures. Signature 16 has only been found in liver cancer tumors, but it was in a higher number in smokers' damaged DNA than in those of non-smokers. It's correlation to smoking is also unknown.
The researchers took into account the pack years smoked (1 pack year = one pack of cigarettes per day per year) and found a positive correlation between pack years and the number of mutational signatures. This information helped them calculate the mutations caused by smoking for each cancer type in the tumors they researched. The results were that one pack year leads to 150 mutations in a lung cell, 97 in a larynx cell, 39 in the pharynx cell, 23 in the oral cavity cell, 18 in the bladder cell, and 6 in a liver cell.
I think that this information is very important for the public, so that it can bring better awareness to how harmful smoking is and how important it is to help treat people with smoking addictions. I hope that more answers can be found about how the signatures mentioned in the previous paragraph cause cancer and what the correlation between these mutations and smoking is, because this information can also help identifying the causes of other cancers due to these mutations.