Smoking a packet of cigarettes a day for a year causes 150 mutations in lung cells, a report out last night revealed.
In the first comprehensive analysis of the DNA of cancers linked to smoking, researchers at the Wellcome Trust Sanger Institute, UK, the Los Alamos National Laboratory, USA, and colleagues have identified the genetic damage in different organs of the body caused by smoking and several ways in which tobacco smoking causes DNA mutations.
The study, published in Science, revealed that the highest mutation rates were seen in the lung cancers but tumours in other parts of the body also contained these smoking-associated mutations, explaining how smoking causes many types of human cancer.
Dr Ludmil Alexandrov, first author from Los Alamos National Laboratory, said the study helped to explain why smokers have a higher risk of developing lung cancer.
Smoking has been associated with at least 17 types of human cancer, but the mechanisms by which smoking causes many of these has not been understood.
The research team examined more than 5,000 tumours and compared cancers from smokers with cancers from people who had never smoked.
They found mutational signatures in the smokers’ DNA and counted how many of these particular mutations were found in the different tumours, concluding that on average, smoking a pack of cigarettes a day led to 150 mutations in each lung cell every year.
These mutations represent individual potential start points for genetic damage that can eventually lead to cancer. Although the numbers of mutations within any cancer cell will vary between individuals, the study shows the additional mutational load caused by tobacco.
Dr Alexandrov said: “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.”
The study also revealed that smoking a packet of cigarettes a day led to an estimated average 97 mutations in each cell in the larynx, 39 mutations for the pharynx, 23 mutations for mouth, 18 mutations for bladder, and six mutations in every cell of the liver each year.
The team also discovered at least five distinct processes of DNA damage due to cigarette smoking.
David Phillips, professor of environmental carcinogenesis at King’s College London, UK, said: “The results are a mixture of the expected and unexpected, and reveal a picture of direct and indirect effects. Mutations caused by direct DNA damage from carcinogens in tobacco were seen mainly in organs that come into direct contact with inhaled smoke. In contrast, other cells of the body suffered only indirect damage, as tobacco smoking seems to affect key mechanisms in these cells that in turn mutate DNA.”
Professor Sir Mike Stratton, joint lead author from the Wellcome Trust Sanger Institute, Cambridge, UK, added: “The genome of every cancer provides a kind of ‘archaeological record’, written in the DNA code itself, of the exposures that caused the mutations that lead to the cancer.
“Our research indicates that the way tobacco smoking causes cancer is more complex than we thought. This study of smoking tells us that looking in the DNA of cancers can provide provocative new clues to how cancers develop and thus, potentially, how they can be prevented.”
Science 3 November 2016
Leave a Reply