New data suggests that random, unpredictable DNA copying mistakes account for nearly two-thirds of the mutations that cause cancer.

Researchers from Johns Hopkins Kimmel Cancer Center reported the findings based 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,” Cristian Tomasetti, Ph.D., assistant professor of biostatistics at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health, said in a statement. “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.

“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.”

Dr. Bert Vogelstein, co-director of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center, explained that there is a push to get the public to better understand the risk of cancer.

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“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” Vogelstein said in a statement. “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.”

According to the research team, the conclusions are in accord with epidemiologic studies that show that approximately 40 percent of cancers can be prevented by avoiding unhealthy environments and lifestyles.

Among the factors driving the new study is that cancer often strikes people who follow all the rules of healthy living and have no family history of the disease, which led to the researchers question whether random DNA copying errors is the cause.

While current and future efforts to reduce known environmental risk factors will have an impact on reducing cancer incidences, 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,” Vogelstein said.

In a previous study Tomasetti and Vogelstein reported that DNA copying errors could explain why certain cancers in the U.S. like colon cancer occur more commonly than other cancers including brain cancer.

However, to examine what fraction of mutations in cancer are due to copying errors the researchers took a closer look at the mutations that drive abnormal cell growth among 32 cancer types. They developed a new mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it takes two or more critical gene mutations for cancer to occur and in a person these mutations can be due to random DNA copying errors, the environment or inherited genes.

Their mathematical model shows that when critical mutations in pancreatic cancers are added together, 77 percent of them are due to random DNA copying errors, 18 percent due to environmental factors like smoking and 5 percent are because of heredity.

In other cancers including prostate, brain or bone, more than 95 percent of the mutations are due to random copying errors.

However, in lung cancer, 65 percent of all the mutations are due to environmental factors, mostly smoking and 35 percent are due to DNA copying errors.

In total 66 percent of cancer mutations result from copying errors, 29 percent can be attributed to lifestyle or environmental factors and 5 percent are inherited in the 32 cancer types studied.

The pair of researchers reasoned that the more cells divide, the higher the potential for copying mistakes in the DNA of cells in an organ.

Tomasetti said that these random DNA copying errors will only get more important as societies face aging populations, prolonging the opportunity for cells to make more and more DNA copying errors and because these errors contribute to a large fraction of cancer, Vogelstein said that people with cancer who have avoided known risk factor should be comforted by their findings.