Most cancers are caused by bad luck, random mistakes that occur when cells divide.
The findings challenge the widespread view that cancer mutations are generally inherited or triggered by environmental factors. Instead, the vast majority of cancers are probably down to defects that occur out of the blue, researchers suggest.
The rate that is down to randomness can be as high as 95 per cent for certain cancers such as brain and prostate. However, in lung cancer it is as low as 35 per cent. Dr Cristian Tomasetti, from Johns Hopkins Kimmel Cancer Center in the US, said: ‘It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer.
‘But it is not as well-known that each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes. ‘These copying mistakes are a potent source of cancer mutations that historically have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.’
Asked at a news conference why this had never been noticed before, he said: ‘Part of the answer is it has never been measured before. ’The research, published in the journal Science, indicates that almost two-thirds of cancer-causing mutations are due to DNA copying errors. The discovery helps explain why cancer often strikes people who follow all the rules of healthy living and have no family history of the disease. The team studied mutations that drive abnormal cell growth in 32 types of cancer.
Using DNA sequencing and epidemiological data, they developed a mathematical system of assessing the role of genetic copying errors in cancer. The results showed that it generally took two or more critical gene mutations to trigger cancer. In some cancer types, such as those affecting the prostate, brain and bone, more than 95 per cent of the harmful mutations were due to random DNA copying errors.
Copying mistakes were linked to 77 per cent of pancreatic cancers but only 35 per cent of lung cancers, which were mostly triggered by smoking and other environmental factors. Overall, 66 per cent of cancer mutations resulted from copying errors, 29 per cent from lifestyle or environmental factors, and 5 per cent from inherited genes.
The researchers compared DNA copying errors to ‘typos’ in a manuscript. ‘You can reduce your chance of typographical errors by making sure you’re not drowsy and that your keyboard isn’t missing some keys,’ said one. ‘But typos will still occur because no one can type perfectly.’
Professor Mel Greaves, of the Centre for Evolution and Cancer at The Institute of Cancer Research in London, said: ‘We have good evidence to show that cancer is caused by a complex mix of environmental exposures, inherited risk, and random chance. ‘And while the genes we inherit from our parents are unreturnable and many chance events are non-negotiable, fortunately for us, exposures are major contributors to our risk of cancer and offer a route to risk reduction or prevention.’