Smoking 20 cigarettes a day for one year racks up 150 genetic mutations in every cell in the lungs, a study has found.
Over time, the accumulating damage can overwhelm the body’s DNA repair systems and lead to cancer.
The study, the first attempt to quantify the genetic damage inflicted by tobacco, also measured the harm smoking causes other organs.
In the course of a year, a 20-a-day habit was found to produce an average of 97 mutations in each cell in the larynx (voice box), 39 mutations in the pharynx (top part of the throat), 23 in the mouth, 18 in the bladder and six in the liver.
Smoking, which claims the lives of at least six million people worldwide each year, has been linked to at least 17 different types of human cancer.
The disease is triggered by mutations - changes in the genetic programming written in DNA - that can cause cells to become “immortal” and multiply uncontrollably.
An international team of scientists, including British researchers from the Wellcome Trust Sanger Institute in Hinxton, Cambridgeshire, analysed DNA from more than 5,000 cancer tumours, comparing those from smokers and non-smokers.
Their findings are published in the journal Science.
Lead author Dr Ludmil Alexandrov, from Los Alamos National Laboratory in the US, 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.”
‘Signatures’
At least five mutational “signatures” linked to smoking-related cancers were identified. Some cancers had more than one of the molecular fingerprints.
One sub-group of mutations, Signature 4, could be traced to damage from direct exposure to tobacco smoke chemicals, especially a specific version of the hydrocarbon benzopyrene.
Another, Signature 5, was thought to speed up a cellular “clock” that accelerated the pace at which natural mutations occurred at regular intervals.
The more often mutations appeared, the more likely it was they would trigger cancer.
Some of the underlying mechanisms by which smoking indirectly increases the risk of cancer remain unclear.
Prof Mike Stratton, from the 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.”
There was little evidence that smoking affected the activity of genes without altering the genetic code itself.
PA