Scientists have measured the catastrophic genetic damage caused by smoking in different organs of the body and identified several different mechanisms by which tobacco smoking causes mutations in DNA.
Now researchers find smokers accumulated an average of 150 extra mutations in every lung cell for each year of smoking one packet of cigarettes a day.
Reported in the Journal Science, the study provides a direct link between the number of cigarettes smoked in a lifetime and the number of mutations in the tumor DNA.
The highest mutation rates were seen in the lung cancers but tumors in other parts of the body also contained these smoking-associated mutations, explaining how smoking causes many types of human cancer.
Tobacco smoking claims the lives of at least six million people every year and, if current trends continue, the World Health Organization predicts more than 1 billion tobacco-related deaths in this century.
Smoking has been epidemiologically associated with at least 17 types of human cancer, but until now no-one has seen the mechanisms by which smoking causes many of these cancer types.
Cancer is caused by mutations in the DNA of a cell.
In the first comprehensive analysis of the DNA of cancers linked to smoking, researchers studied over 5,000 tumors, comparing cancers from smokers with cancers from people who had never smoked.
They found particular molecular fingerprints of DNA damage – called mutational signatures – in the smokers’ DNA, and counted how many of these particular mutations were found in the different tumors.
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 individual potential start points for a cascade of genetic damage that can eventually lead to cancer.
The numbers of mutations within any cancer cell will vary between individuals, but 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 6 mutations in every cell of the liver each year.
Until now, it has not been fully understood how smoking increases the risk of developing cancer in parts of the body that don’t come into direct contact with smoke.
However, the study revealed different mechanisms by which tobacco smoking causes these mutations, depending on the area of the body affected.
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, tobacco smoking seems to accelerate the speed of a cellular clock that mutates DNA prematurely.
Citation: Alexandrov L, et al. (2016). Mutational signatures associated with tobacco smoking in human cancer. Science, published online. DOI: 10.1126/science.aag0299.
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