Random, unpredictable DNA copying "mistakes" account for nearly two-thirds of the mutations that cause cancer, according to a new study which explains why people with healthy lifestyle are still stricken with the deadly disease. The findings by researchers at Johns Hopkins Kimmel Cancer Centre in the US are based on genetic sequencing and cancer studies from 69 countries around the world. The study confirms that too little scientific attention is given to early detection strategies that would address the large number of cancers caused by random DNA copying errors.
"These cancers will occur no matter how perfect the environment," said researchers who used a novel mathematical model for the study. "It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer," said Cristian Tomasetti, assistant professor at Johns Hopkins Kimmel Cancer Centre.
"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 Tomasetti. "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," he said. Researchers said their conclusions are in accord with epidemiologic studies showing that about 40 per cent of cancers can be prevented by avoiding unhealthy environments and lifestyles.
However, among the factors driving the new study, said the researchers, is that cancer often strikes people who follow all the rules of healthy living - nonsmoker, healthy diet, healthy weight, little or no exposure to known carcinogens - and have no family history of the disease, prompting the pained question "Why me?" "We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations," Bert Vogelstein, from Johns Hopkins Kimmel Cancer Centre. "However, 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," Vogelstein said.
The scientists took a close look at the mutations that drive abnormal cell growth among 32 cancer types. They said it generally takes two or more critical gene mutations for cancer to occur. In a person, these mutations can be due to random DNA copying errors, the environment or inherited genes. Researchers used a mathematical model to show, for example, that when critical mutations in pancreatic cancers are added together, 77 per cent of them are due to random DNA copying errors, 18 per cent to environmental factors, such as smoking, and the remaining 5 per cent to heredity. The study was published in the journal Science.
