Smoking a pack of cigarettes a day causes an average of 150 mutations a year in lung cells, according to a new study that identifies specific ways smoke exposure damages DNA.
The research, published in the journal Science, analyses and compares tumours, providing the first accurate measure of the devastating genetic damage smoking inflicts not only in lungs but also in other organs not directly exposed to smoke.
Although it was previously known that smoking contributes to at least 17 types of human cancers, it had remained unclear exactly how cigarettes caused tumours, according to the researchers from Britain's Wellcome Trust Sanger Institute and the Los Alamos National Laboratory in the United States.
Although they saw the largest number of genetic mutations in lung tissue, other parts of the body also displayed changes in DNA, helping explain how smoking causes various types of cancer.
Cigarettes contain more than 7,000 different chemicals, of which 70 are known to be carcinogenic, the researchers said, pointing to the complexity of how smoke interacts with the body.
"This study offers fresh insights into how tobacco smoke causes cancer," said Ludmil Alexandrov of the Los Alamos National Laboratory, one of the study's main co-authors.
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"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," he added.
"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."
Variation between people
In the first comprehensive analysis of the DNA of cancers linked to smoking, the scientists studied more than 5,000 tumours, comparing smokers' cancers with those of people who had never smoked.
They found specific molecular features of damage in the smokers' DNA, determined by the number of those mutations in different tumours.
Although the number of mutations within cancer cells varies between people, the new study identifies the additional "mutational load" tobacco smoking causes.
In other affected organs, the study shows smoking a pack a day causes an estimated average of 97 mutations in each cell of the larynx; 39 in the pharynx; 23 in the mouth; 18 in the bladder; and six mutations in every cell of the liver each year.
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The research shows at least five distinct ways smoking damages DNA, the most common of which is found in most types of cancer: accelerating the speed of a cellular clock that appears to mutate DNA prematurely.
"Our research indicates that the way tobacco smoking causes cancer is more complex than we thought," Mike Stratton of Wellcome Trust Sanger Institute said.
Largest preventable cause of death
"Indeed, we do not fully understand the underlying causes of many types of cancer," he added, pointing to other known causes, such as obesity.
But the new study of smoking-related cancers can help scientists better understand how all cancers develop and, possibly, how they can be prevented, Stratton said.
"The genome of every cancer provides a kind of 'archaeological record', in the DNA code, reflecting the exposure that causes mutations," he added.
Smoking – the largest preventable cause of death – is responsible for at least six million deaths a year worldwide.
If current trends continue, the World Health Organisation says, smoking will kill more than a billion people in the 21st century.
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