Are two-thirds of cancers due to ‘bad luck’?

"This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors," says Bert Vogenstein. "However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors." (Credit: iStockphoto)

A new statistical model suggests that almost two-thirds of adult cancer types could be explained primarily by the “bad luck” of random mutations in the patients’ genes, rather than environmental factors or inherited traits.

“Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their ‘good genes,'” says Bert Vogelstein, a professor of oncology at the Johns Hopkins University School of Medicine and investigator at the Howard Hughes Medical Institute.

“But the truth is that most of them simply had good luck,” Vogelstein says.

But don’t smoke or overeat

That is no reason, however, to start smoking, drinking, overeating, or making other bad lifestyle choices. Vogelstein cautions that poor lifestyles do help trigger a significant number of cancer cases—and particularly certain types of cancer—and can amplify the bad luck factor in cancer development.

The statistical model built by Vogelstein and his research teammate does, however, suggest a need to reconsider priorities in cancer research funding and cancer education and prevention programs.

“If two-thirds of cancer incidence across tissues is explained by random DNA mutations … then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others,” says co-researcher Cristian Tomasetti, a biomathematician and assistant professor at the Johns Hopkins Kimmel Cancer Center.

“We should focus more resources on finding ways to detect such cancers at early, curable stages,” he adds.

Stem cell divisions

In a report published in Science, the scientists note that they did not include some cancers, such as breast and prostate cancer, in their analysis, because they could find no reliable stem cell division rates for those tissues in the scientific literature. They hope that future research will help refine their statistical model with more precise cell division rates for such parts of the body.


Cancer can arise when tissue-specific stem cells copying DNA during cell division make random mistakes, or mutations, in genes that can drive cancer growth. The more mutations accumulate, the higher the risk that cells will grow unchecked, a hallmark of cancer.

Though this process has long been known, the actual contribution of the random mistakes to cancer incidence, in comparison to hereditary or environmental factors, has not, Vogelstein says.

The Johns Hopkins scientists charted the known rate of stem cell divisions in 31 tissues and compared them with the lifetime risk among Americans of cancer in the same tissues.

“Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue,” Vogelstein says. For example, colon tissue undergoes four times more stem cell divisions than small intestine tissue in humans. Likewise, colon cancer is much more prevalent than small intestinal cancer.

“You could argue that the colon is exposed to more environmental factors than the small intestine, which increases the potential rate of acquired mutations,” Tomasetti says. But mice have a lower rate of stem cell divisions—and lower cancer incidence—in their colons than in their small intestines. The scientists say this supports the key role of the total number of stem cell divisions in the development of cancer.

Using statistical theory, the pair calculated that about 65 percent of the variation in cancer risk can be explained by the number of stem cell divisions. They also classified the types of cancer they studied into two groups. They calculated which types had an incidence predicted by the number of stem cell divisions and which had higher incidence.

Bad luck plus other factors

They found that 22 cancer types could be largely explained by the “bad luck” factor of random DNA mutations during cell division. The other nine cancer types had incidences higher than predicted by “bad luck” and were presumably due to a combination of bad luck plus environmental or inherited factors.

“We found that the types of cancer that had higher risk than predicted by the number of stem cell divisions were precisely the ones you’d expect, including lung cancer, which is linked to smoking; skin cancer, linked to sun exposure; and forms of cancers associated with hereditary syndromes,” Vogelstein says.

“This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors,” Vogelstein adds. “However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors.

“The best way to eradicate these cancers will be through early detection, when they are still curable by surgery.”

The Virginia and D. K. Ludwig Fund for Cancer Research, the Lustgarten Foundation for Pancreatic Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, and the National Institutes of Health’s National Cancer Institute funded the research.

Source: Johns Hopkins University