DNA Copying Errors Could Be the Most Common Cause of Cancer

Ewa Krawczyk, National Cancer Institute / Georgetown Lombardi Comprehensive Cancer Center, National Institutes of Health via Flickr Creative Commons // CC BY-NC 2.0

 
Researchers say the majority of cancer-causing mutations may not be the result of environmental factors or heredity, but of errors created in the DNA replication process. They published their findings in the journal Science.

Cancer arises when something goes wrong in the body’s cells. They start dividing, as normal cells do, but then they don’t stop. There are three reasons this might happen. First, a person might inherit genes that are pre-programmed to kick off this abnormal cell division. Second, exposure to harmful substances like cigarette smoke, sunlight, or alcohol puts a strain on the body and damages a person’s DNA, increasing the risk that mutations will arise.

The third reason—faulty DNA copying—is less well known and has generally been considered less of a problem than heredity or environmental factors.

But the authors of the new paper say we’ve got it all backward. They examined cancer-causing mutations in 17 different cancers, including pancreatic, bone, lung, and prostate, and identified the mutations most likely to cause each cancer type. Then they created a mathematical model using records of real cancer incidence in 69 countries around the world—representing 4.8 billion people, or two-thirds of the world's population—and genetic samples from people with cancer.

Their results varied by cancer type. The mutations leading to lung cancer were, as previously believed, most likely to be caused by environmental factors like smoking. But other cancers were far more likely to arise from copying errors. The likelihood of pancreatic cancer being caused by DNA replication mistakes was 77 percent; for prostate, bone, and brain cancers, the number was as high as 95 percent.

C. Tomasetti et al,. Science (2017).

 
Co-author Bert Vogelstein of the Johns Hopkins Kimmel Cancer Center says his team’s results should lead to a big shift in the way we think about cancer risk, diagnosis, and treatment.

“You can reduce your chance of typographical errors by making sure you're not drowsy while typing and that your keyboard isn't missing some keys. But typos will still occur because no one can type perfectly," he said in a statement. "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.”