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Breakthroughs

How DNA Mistakes Cause Cancer

By Julie Scharper
DNA
Cristian Tomasetti is a biostatistician and Bert Vogelstein a cancer geneticist at the Johns Hopkins Kimmel Cancer Center.

What causes cancer? Smoking? An unhealthy diet? Exposure to radiation or pollutants? A new study from Johns Hopkins researchers indicates that simple bad luck plays a key role.

Two-thirds of the mutations found in cancers arise from random mistakes during cell division, Cristian Tomasetti, a Cristian Tomasetti is a biostatistician and Bert Vogelstein a cancer geneticist at the Johns Hopkins Kimmel Cancer Center. biostatistician at the Kimmel Cancer Center and Bloomberg School of Public Health, and Bert Vogelstein, a cancer geneticist and co-director of the Kimmel Cancer Center’s Ludwig Center, stated in 2017 in the journal Science.

Mutations are a normal part of cellular reproduction, and, in fact, they are the engine of evolution. They occur during the course of normal cell division, with as many as 2 trillion cells dividing in our bodies every day. Random mutations cause new traits to arise within a species. If these traits help an animal adapt to its environment—allowing them to better evade predators, for example—they’ll be more likely to have offspring and pass the trait to the next generation. Over time, the new trait becomes more prevalent as the species evolves.

“If cell replication were perfect, we wouldn’t be having this conversation,” Vogelstein says. “We’d all be amoebas. The reason that we’re here is that all cells make mistakes as they divide.”

But occasionally these mutations lead cells to become cancerous. Scientists have long known that some mutations arise spontaneously, while others are influenced by genetics or risk factors such as smoking. Tomasetti and Vogelstein are the first to assign probabilities to these three scenarios.

“We don’t want people to feel guilty that they have cancer,” says Vogelstein, who previously trained as a pediatrician. He recalls having met with parents whose despondency over their child’s cancer included thoughts of blaming themselves: Had they passed along faulty genes or unwittingly exposed their child to carcinogens? “The knowledge that there’s a third way that people get cancer should help people feel better,” he says. “These are unavoidable mutations—a side effect of evolution.”

Some in the public health community worry that these findings could discourage people from taking precautions to lower their risk of developing cancer. The researchers caution that lifestyle does influence cancer risk. A diet rich in fruits and vegetables, regular exercise, and avoiding carcinogens such as cigarette smoke can significantly reduce the chance of cancer. Taking these precautions is like buckling your seat belt. While a seat belt doesn’t prevent all traffic deaths, it dramatically lowers the odds that you’ll die in an accident.

Some cancers—including those of the blood, brain, and prostate—are more likely to arise from random mutations, while others, such as lung cancer, are more likely to be caused by environmental or lifestyle factors, according to the study.

Exposure to carcinogens and other risk factors increases the pace of mutations within cells. Tomasetti compares the process to typing a lengthy manuscript. Some typos are all but certain. But if you type on a faulty keyboard, or work when you’re exhausted, you’ll be more likely to make mistakes.

The researchers identified four different ways that random replicative mutations arise. If scientists could find a way to slow or halt the processes that lead to these mutations, they could theoretically reduce the incidence of cancer, Vogelstein says.

Tomasetti and Vogelstein already have several related studies underway. One examines the specific signatures of factors that cause mutations.

“If I analyze the lung tissue of a smoker, I can see different mutation patterns than in a nonsmoker,” Tomasetti says. “Different factors leave different mutation signatures. We want to determine which factors specifically caused a patient’s mutation.”

They are also working to apply their research to bolster early detection. While some cancers are unavoidable, Tomasetti says, the effects can be minimized through early detection.

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Illustration above by Colin Johnson; Illustration to the left by Wenjia Tang
As many as 2 trillion cells divide in our bodies every day, and a new study suggests that random mutations in those cells account for many cancers.

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