WASHINGTON • More than two- thirds of cancer-causing mutations are the result of random mistakes in DNA replication that occur when normal cells divide, according to a paper just published.
The study is sure to renew a vigorous debate over how much individuals can do to prevent cancer and how much is unavoidable.
The researchers, mathematician Cristian Tomasetti and cancer geneticist Bert Vogelstein, both from Johns Hopkins University, set out to determine what proportion of cancer mutations are due to unpredictable DNA-copying errors - as opposed to the two other main contributors to cancer, inherited genes and environmental factors such as smoking and obesity.
For their study, published in Science on Thursday, the scientists used a mathematical model that analysed genome sequencing and epidemiological data for 32 types of cancer. Overall, they concluded, 66 per cent of mutations that contribute to cancer are due to unavoidable DNA-replication mistakes, while 29 per cent are attributable to environmental factors and 5 per cent to heredity.
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CANCER GENETICIST BERT VOGELSTEIN, on the need to detect cancer early in order to increase the chances of effectively treating the disease should such random mutations occur.
That does not mean that two- thirds of cancer cases are caused by random copying errors, they said; It can take three, four or more mutations to make a cell turn malignant. Moreover, the proportion of mutations due to random copying errors varies, depending on the cancer, said the researchers.
Random DNA-replication mistakes account for about 77 per cent of critical mutations in pancreatic cancer, and virtually all of those in childhood cancer, they said.
In contrast, they noted, more than two-thirds of the mutations in lung cancer arise from environmental factors, mostly smoking.
Humans have trillions of cells, which are constantly regenerating through the division and creation of new cells. But each time DNA is copied, said the scientists, an average of three random mistakes will occur.
Most of them are harmless, but a small number affect genes that will promote cancer.
The new research builds on a 2015 study that highlighted the role of "bad luck" - random DNA errors - in developing cancer. That study drew vehement protests from some cancer physicians and researchers, who feared it would encourage people to take a fatalistic approach to cancer, rather than trying to reduce their cancer risk by maintaining a healthy weight, exercising regularly, adopting a good diet and avoiding cigarettes.
The Hopkins researchers have said their earlier work was widely misinterpreted. Nevertheless, in a news briefing earlier this week, they took pains to stress that their study was consistent with estimates that 40 per cent of cancers can be prevented, and urged the public to pursue healthy lifestyles.
But they also said it was important for scientists and the public to recognise that a large percentage of cancer mutations occur no matter how pristine the environment or how laudable someone's lifestyle choices.
"Most of the enemies are inside us - they are already here," Dr Vogelstein said, referring to the random cancer-causing mutations. He said that science needs to find better ways to detect cancer early, when there is a greater chance of overcoming it.