A new study found that more than two-thirds of cancer-causing mutations are the result of random DNA-copying mistakes when normal cells divide. (Cancer cell illustration by iStock)
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 published Thursday. The study is sure to renew a vigorous debate over how much people can do to prevent cancer and how much is unavoidable.
The researchers, mathematician Cristian Tomasetti and cancer geneticist Bert Vogelstein, both of 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, the scientists used a mathematical model that analyzed genome sequencing and epidemiological data for 32 types of cancer. Overall, they concluded, 66 percent of mutations that contribute to cancer are due to unavoidable DNA-replication mistakes, while 29 percent are attributable to environmental factors and 5 percent to heredity. That doesn't 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, the researchers said. Random DNA-replication mistakes account for about 77 percent of critical mutations in pancreatic cancer, and virtually all childhood cancer, they said. By contrast, they concluded that more than two-thirds of the mutations in lung cancer were due to environmental factors, mostly smoking.
Humans have trillions of cells, which are constantly regenerating by dividing and making new cells. But each time DNA is copied, the scientists said, an average of three random mistakes will occur. While most are harmless, 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 worried 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, eating 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 percent of cancers can be prevented, and urged the public to pursue healthy lifestyles.
But they also said it is important for scientists and the public to recognize 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,” 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 curing it.