A new study has found that up to 66 percent of cancer-causing mutations can be attributed to random mistakes made during DNA replication.
US scientists analysed cancer incidence data from 69 different countries and concluded environmental and hereditary factors account for 29 percent and five percent of cancer-causing mutations, respectively.
'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,' said Dr Cristian Tomasetti from John Hopkins Kimmel Cancer Centre and co-author of the study. He added: 'This new work provides the first estimate of the fraction of mutations caused by these mistakes.'
The study was a follow up of the authors' previous study (see BioNews 785) in which they used a mathematical modelling technique to compare estimated numbers of stem cell divisions in a particular organ with the lifetime incidence of organ-specific cancer development, and found a strong correlation.
This latest study included the analysis of 32 different types of cancer (including breast and prostate), with data collected across 69 countries in the world, whereas the previous study had only used data from the US.
The authors looked for mutations in cancer data that indicated environmental factors, and found two-thirds of mutations could be attributed to random errors from DNA replication.
They estimated stem cell division rates in different human tissues and compared this to incidence of 17 cancer types. They assumed that three mutations – either from DNA copying errors, environmental or hereditary factors – were necessary to cause cancer.
The results showed different ratios of mutations caused by the above factors in different cancers. For example, in pancreatic cancer 77 percent of mutations were due to DNA replication errors, whereas lung cancer mutations were found to be predominantly caused by environmental factors (65 percent) not DNA copying errors (35 percent).
The results support epidemiological data which suggests that 40 percent of cancers are preventable if a healthy lifestyle is followed and environmental risks are avoided, but helps to explain why so many patients who 'follow all the rules' still develop cancer. It's a case of 'bad luck', said Dr Bert Vogelstein of John Hopkins Kimmel Cancer Centre and co-author of the study.
However, Professor Mel Greaves, director of the Centre for Evolution and Cancer at The Institute of Cancer Research, said: '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.'
The authors say the new study confirms that too little scientific attention is given to early detection strategies.
'Many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed,' said Dr Vogelstein.
The study was published in Science.
Sources and References
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DNA typos to blame for most cancer mutations
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Most cancer mutations are due to random DNA copying 'mistakes'
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DNA Copy Roulette Accounts for Most Cancer Mutations
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'Bad luck' mutations increase cancer risk more than behavior, study says
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Two thirds of cancers are unavoidable even if you live a healthy life, study finds
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