Johns Hopkins Kimmel Cancer Center scientists report data from a new study providing evidence that random, unpredictable DNA copying “mistakes” account for nearly two–thirds of the mutations that cause cancer. Their research is grounded on a novel mathematical model based on DNA sequencing and epidemiologic data from around the world.

“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,” says Cristian Tomasetti, PhD, assistant professor of biostatistics at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health. “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.”

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations. 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,” says Bert Vogelstein, MD, co–director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center.

Tomasetti and Vogelstein conducted the new study described in a report published March 24 in the journal Science.

The researchers say their conclusions are in accord with epidemiologic studies showing that approximately 40 percent of cancers can be prevented by avoiding unhealthy environments and lifestyles. But among the factors driving the new study, say 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?”

Tomasetti and Vogelstein believe the answer to this question rests in random DNA copying errors.

Current and future efforts to reduce known environmental risk factors, they say, will have major impacts on cancer incidence in the U.S. and abroad. But they say the new 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,” says Vogelstein.