Scientists have figured out that smoking increases the risk of not just lung cancer but 17 types of cancer. This happens because smoking causes cell mutations in different organs of the body. The latest study shows that smoking a pack of cigarettes causes an additional 150 mutations in every lung cell for each year of smoking.
Other organs that get affected, according to the study, included an average of 97 mutations in each cell in the larynx, 39 mutations for the pharynx, 23 mutations for mouth, 18 mutations for bladder and 6 mutations in every cell of the liver, each year.
Cigarette smoking costs a loss of more than 6 million people each year. Cigarettes contain more than 60 carcinogens, all of which accelerate tumor growth by causing mutations in the tumor DNA.
The scientists analyzed somatic mutations which is the alteration of genes causing them to pass on in cell division and DNA methylation in 5,243 genomes for which tobacco smoking is known to increase risk of cancer.
They studied these cancers and compared them with cancers found in nonsmokers, in order to analyze biophysical differences between the two types, focusing on mutational signatures that vary in different cancers.
Smoking is linked with increased mutation burdens of a variety of different mutational signatures which cause the biologically different effects in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens.
Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clocklike mutational process. However, smoking causes DNA methylation in a limited amount. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation frequency, although clear proof for this mechanism is lacking in some smoking-related cancer types.
Dr Ludmil Alexandrov, first author from Los Alamos National Laboratory, had this to say, “Before now, we had a large body of epidemiological evidence linking smoking with cancer, but now we can actually observe and quantify the molecular changes in the DNA due to cigarette smoking.
With this study, we have found that people who smoke a pack a day develop an average of 150 extra mutations in their lungs every year, which explains why smokers have such a higher risk of developing lung cancer.”
Even though it is a remarkable study in its own, it still remains unclear how exactly smoking causes increase in tumors in other parts of the body that are unaffected by smoke. However, this research points out that different mechanisms are at play by which tobacco smoking causes these mutations, depending on the area of the body affected.
Professor David Phillips, an author on the paper and Professor of Environmental Carcinogenesis at King’s College London, believed that the results were quite fascinating as they were a combination of predicted and unexpected theories, and laid out the direct and indirect effects.
The expected result was that mutations caused by direct DNA damage from carcinogens in tobacco were mostly observed in organs that were in direct contact of tobacco smoke such as mouth and lungs.
In contrast, the unexpected or surprising result was that the other cells of the body suffered from indirect damage, as tobacco smoking seems to affect key mechanisms in these cells that in turn cause DNA mutations, which could be why other organs got affected so frequently.
Consistent with the proposition that an increased mutation load caused by tobacco smoke causes an increased cancer risk, the total mutation burden is higher in smokers compared to nonsmokers, specifically in lung adenocarcinoma, larynx, liver and kidney cancers.
However, differences in total mutation frequency were not observed in the other cancer types linked with smoking and in some there were no statistically significant smoking-associated differences in mutation load, mutation signatures or DNA methylation.
The researchers warned that this does not mean that smokers will be safe from acquiring certain cancers and careful deliberation is required when analyzing such findings. Aside from statistical limitations to thoroughly study the invasive effects of cancer, multiple rounds of clonal expansion over many years are required.
Therefore, it is possible that in the normal tissues from which smoking-associated cancer types originate, there are more somatic mutations or differences in methylation in smokers than in nonsmokers that could have been missed by the scientists as these differences become obscured at the start of clonal evolution, as the immune system has not expanded as such to properly detect the tumors.
Further studies should also involve e-cigarette users as a majority of population is switching to them in the hope of quitting smoking. Teenagers and young adults especially are using e-cigarettes as a form of recreation.
If follow-up studies include e-cigarettes and find similar results of accelerated cancer growth, it is hoped that people will be able to quit smoking altogether in any form.