Scientists have for the first time shown the specific mutations that make smoking cause cancer. By analysing the genomes of 5,243 tumours, an international team of researchers identified mutations associated with tobacco smoke – cancers showed signature characteristics if the tissue involved had been exposed to smoke.
The link between smoking and cancer has been known for many years. It has been linked to an increased risk of 17 different types of cancer. Tobacco contains over 7,000 chemicals, at least 70 of which are known carcinogens (cancer causing). However, exactly how and why smoking causes cancer – ie. the process leading to the disease – is not well understood.
In a study published in Science, researchers were able to look at thousands of cancers related to smoking. They then analysed the tumours and looked if the person was a smoker or not.
"This research brings together Big Data generated by international cancer consortia and the supercomputing and machine-learning capabilities of Los Alamos to address one of the leading public health issues of our time," said Charlie McMillan, director of the Los Alamos National Laboratory.
The carcinogens in cigarettes are believed to lead to DNA damage, which results in more mutations taking place in healthy cells. This is why smokers have an increased risk of cancer.
All biological processes that lead to cell mutations leave behind a signature on the base pair of the cell's genome. This means the cause of the mutation can be traced back. Researchers found over 20 mutation signatures across the 17 cancers that have been associated with smoking. Of these, five were elevated in the tumours of people who smoked.
Specifically, a sub-group of mutations identified as 'Signature 4' was particularly prominent. This mutation directly related to DNA damage on tissue that was directly exposed to smoke, like the lungs and larynx. Other signatures found related to a certain enzyme known to cause mutation by speeding up the molecular clock – these were found where smoke was not directly exposed, like bladder cancer.
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."