What Causes Cancer? Mostly Random ‘Mistakes’ In Copying DNA, Study Finds

Cancer has been among the leading causes of death worldwide, and in the United States it is second only to heart diseases, killing 591,699 people during the year in 2015, according to data from the Centers for Disease Control and Prevention. And it has long been known that an unhealthy lifestyle and environmental factors have a large role to play in causing cancer.

However, a study published Friday by three researchers from Johns Hopkins Medicine tries to address why people with healthy lifestyles also have DNA mutations that lead to cancer. In the study, titled “Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention” and published in the journal Science, they provide evidence that shows about two-thirds of mutations that cause cancer are due to random and unpredictable “mistakes” in copying DNA when normal cells in the body divide.

“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. 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,” Cristian Tomasetti, from the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins Bloomberg School of Public Health, and one of the co-authors of the study, said in a statement Thursday.

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The research supports conclusions from previous epidemiologic studies that show about 40 percent of cancers can be prevented by having a healthy lifestyle. But the main aim of the research was to account for the cause of the large number of cases where people develop cancer despite not smoking, eating healthy, maintaining a healthy weight, having little to no exposure to known carcinogens, and without any family history of the disease.

Referring to cancers caused by random DNA mutations, Bert Vogelstein, from the Ludwig Center at the Johns Hopkins Kimmel Cancer Center, and also a co-author on the paper, said in the statement: “These cancers will occur no matter how perfect the environment.”

For the study, the researchers looked at DNA mutations in 32 different types of cancer and developed a new mathematical model to analyze the DNA sequencing data. They found, in the case of pancreatic cancer, that 77 percent mutations occurred due to random DNA copying errors, 18 percent were caused by environmental factors and 5 percent were hereditary in nature.

Some cancer types — like prostrate, brain or bone — showed as high as over 95 percent incidence of random mutations being responsible for cancer, while some others — like lung — showed only 35 percent mutations caused by DNA copying 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,” Vogelstein said.