Researchers reveal why cigarettes damage organs in the body

Researchers have sought to understand why smoking increases the risk of developing cancer in parts of the body that don’t come into direct contact with smoke.

The study, by the Wellcome Trust Sanger Institute, provides a direct link between the number of cigarettes smoked in a lifetime and the number of mutations in the tumour DNA.

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.

Tobacco smoking is responsible for the deaths of at least six million people every year and, if current trends continue, the World Health Organisation predicts more than 1 billion tobacco-related deaths this century.

Smoking has been associated with at least 17 types of human cancer, but until now no-one has seen how smoking causes many of these cancer types.

Dr Ludmil Alexandrov, first author from Los Alamos National Laboratory, 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.”

Cancer is caused by mutations in the DNA of a cell.

Researchers have studied over 5,000 tumours, comparing cancers from smokers with cancers from people who had never smoked.

They found mutations in the smokers’ DNA, and counted how many of these particular mutations were found in the different tumours.

The authors found that, on average, smoking a pack of cigarettes a day led to 150 mutations in each lung cell every year.

These mutations represent starting points for genetic damage that can eventually lead to cancer. The numbers of mutations within any cancer cell will vary between individuals, but experts said this study shows the additional mutational load caused by tobacco.

Other organs were also affected, with the study showing that a pack 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.

Professor David Phillips, an author on the paper and Professor of Environmental Carcinogenesis at King’s College London, said: “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.”

The study revealed at least five distinct processes of DNA damage due to cigarette smoking. The most widespread of these is a mutational signature already found in all cancers.

In this case, experts found tobacco smoking seems to accelerate the speed of DNA mutations.

Professor Sir Mike Stratton, joint lead author from the Wellcome Trust Sanger Institute, said: “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.

“Indeed, we do not fully understand the underlying causes of many types of cancer and there are other known causes, such as obesity, about which we understand little of the underlying mechanism.

“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.”


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