Nearly Two-Thirds of Cancer-Causing Mutations Are Unavoidable, Study Claims

But it’s complicated—and the medical community is not in agreement about the new findings

Cancer cells in culture from human connective tissue, illuminated by darkfield amplified contrast. National Cancer Institute/Wikimedia Commons

In 2015, researchers Christian Tomasetti and Bert Vogelstein published a study in the journal Science, suggesting that unavoidable, random mutations of healthy stem cells play a significant role in determining whether or not a person gets cancer—more so than hereditary genetics or environmental factors. But medical professionals swiftly skewered their findings, attacking the researchers’ methodology, and accusing Tomasetti and Vogelstein of undermining the importance of cancer prevention.

Now, Richard Harris reports for NPR, the duo is back with a second study, also published in the journal Science, that seeks to clarify their previous research—and lend credence to their original findings.

Vogelstein explained during a press conference that DNA mutations occur every time a cell divides. For the most part, these mutations occur in unimportant parts of the DNA. But every now and then, they “occur in a cancer driver gene,” Vogelstein said, according to Harris. “That's bad luck.”

If cancer driver genes get mutated two or three times within the same cell, they can cause the cell to become cancerous. The study concludes that 66 percent of cancerous mutations are caused by “bad luck”—or random errors in healthy cells. Environmental factors, like smoking and chemical exposure, account for 29 percent of cancerous mutations, according to the study. Hereditary factors are responsible for the remaining five percent.

The 2015 paper by Tomasetti and Vogelstein came under fire for excluding certain types of cancers—like breast cancer and prostate cancer—and for only considering data from U.S. patients, George Dvorsky reports for Gizmodo. This time around, the team used a “new mathematical model” to evaluate 32 cancer types, relying on international data. Researchers compared the number of cell divisions occurring in patients from 68 countries, and found a close link between cancer incidence and cell mutations that were not influenced by heredity or environmental factors.

The new paper also determines the proportion of mutations caused by DNA copying errors—something that the previous study did not do. “This new paper is the first time that anyone has looked at proportions of mutations in any cancer type and assigned the three causal factors,” Tomasetti told Dvorsky. “I consider this a completely new result compared to our previous one.”

Importantly, as Sharon Begley points out for Scientific American, the study does not claim that 66 percent of all cancers are caused by bad luck mutations. Instead, it suggests that about two-thirds of the difference in cancer rates among various types of tissue can be explained by the rate at which cells randomly divide in those tissues. As an example, Begley notes that approximately five percent of people develop cancer of the large intestine, where cells divide at a high rate. But only 0.2 percent of people get cancer of the small intestine, where cells divide fare less frequently.

“[T]he cause of many cancers might be environmental factors,” Begley writes. “But the difference in cancer rates in different tissues can still be the result of different underlying rates of cell division.” 

Tomasetti and Vogelstein’s study did indeed find that bad luck mutations do not affect all types of cancer equally, as Harris notes for NPR. Lung cancer, the study says, is overwhelmingly caused by environmental factors. Most pediatric cancers, on the other hand, are the result of random mutations.

When asked what people can do to curb natural mutations of cancerous cells, Vogelstein gave a rather disheartening response. “Nothing,” he said, according to Harris. “Right now, nothing.”

Despite the improvements to their methods, the team’s recent findings have already been subjected to criticism. Dr. Graham Colditz, an epidemiologist at Washington University in St. Louis, told Harris that the interplay of genetic, hereditary, and environmental factors in causing cancer is too “complex” to untangle into three neat categories. Song Wu, an Associate Professor at Stony Brook University’s Department of Applied Mathematics and Statistics, told Gizmodo’s Dvorsky that the study’s “conclusions are somewhat too bold.”

It’s also important to note that Tomasetti and Vogelstein’s conclusions do not imply that cancer prevention is pointless. “Primary prevention is the best way to reduce cancer deaths,” the researchers write in their study—meaning that it is still of vital importance to eat right, maintain a healthy weight, and steer clear of harmful chemicals. The study also highlights the importance of secondary prevention, or early detection and treatment. Because, as Tomasetti and Vogelstein write, “[f]or cancers in which all mutations are the result of [random mutations], secondary prevention is the only option.”

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