While environmental factors and genetics play a role in the development of cancer, scientists at Johns Hopkins University have used statistical modeling to show that two-thirds of adult cancers may be attributable to "bad luck," or random mutations, rather than lifestyle.

Researchers Bert Vogelstein M.D. (Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute) and Cristian Tomasetti PhD (assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health) charted the number of stem cell divisions in 31 tissue types and compared them with the lifetime risks of cancer in the same tissues among Americans.

Stem cells "self-renew," meaning they repopulate cells that die off in a specific organ. Cancer occurs when tissue-specific stem cells make random mistakes, or mutations.The more mutations, the higher the risk of cancer, however it was not previously known how these random mutations contribute to cancer compared to genetic or environmental factors.

"All cancers are caused by a combination of bad luck, the environment and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development," says Vogelstein.

Vogeltsein and Tomasetti determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated. Using statistical theory, they calculated that approximately 65 percen of the variation in cancer risk can be explained by the number of stem cell divisions.

Of the pair tissue types studied, the researchers found that 22 cancer types, including head and neck, esophageal, gallbladder and some bone cancers, can 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, so are presumably due to a combination of bad luck as well as environmental or genetic factors. These include lung cancer, which is linked to smoking, and skin cancer, which is linked to sun exposure.

Vogelstein and Tomasetti use the analogy of a car accident to help explain their results. "Our results would be equivalent to showing a high correlation between length of trip and getting into an accident," they say. "The longer the trip is, the higher the risk of an accident."

They liken road conditions en-route to the destination to the environmental factors in cancer. Worse conditions are associated with a higher risk of an accident. The mechanical condition of the car is a metaphor for inherited genetic factors. Mechanical problems in the car, such as bad brakes and worn tires, increase the risk of an accident. The more mechanical defects, the greater the risk. Similarly, the amount of inherited genetic mutations contributes to cancer risk.

The length of the trip can be compared to the stem cell divisions and random mutations Vogelstein and Tomasetti discuss in their paper. Regardless of road and car conditions, the probability of an accident increases with distance traveled. Short trips have the lowest risk, while long trips are associated with the highest risk.

"Using this analogy, we would estimate that two-thirds of the risk of getting into an accident is attributable to the length of the trip," say the scientists.

However, they emphasize that "no single factor causes cancer" and poor lifestyles can add to the bad luck factor in the development of cancer. "This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors."

To use their car analogy, the fact that much of the risk of traveling by car is due simply to the trip distance doesn't mean that accidents can't be prevented (or at least the risk reduced). Even if the distance of a trip can't be changed, the journey can be made safer by driving well-maintained vehicles, using seat belts and airbags, and choosing a particular route.

Likewise, there are many opportunities for cancer prevention. Eliminating environmental factors where possible, for example, and adopting a healthier lifestyle.

Vogelstein and Tomasetti say the best way to prevent deaths from other cancer types is to detect them and treat them early, while they are still curable. The implications of their model range from altering public perception about cancer risk factors to the funding of cancer research.

The findings have been published in a recent issue of Science.

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