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Study Points to Number of Stem Cell Divisions as Reason for Variation in Cancer Risk Among Tissues

Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Now scientists from the Johns Hopkins Kimmel Cancer Center have created a statistical model that measures the proportion of cancer incidence, caused mainly by random mutations that occur when stem cells divide.

“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,” said Bert Vogelstein, M.D., a 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. “This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors. 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,” he added.

The implications of the model range from altering public perception about cancer risk factors to the funding of cancer research, according to the research team.

“If two thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, 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,” said co-investigator Cristian Tomasetti, Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. “We should focus more resources on finding ways to detect such cancers at early, curable stages.”

In a report on the statistical findings, published January 2 in Science, Drs. Tomasetti and Vogelstein say they came to their conclusions by searching the scientific literature for information on the cumulative total number of divisions of stem cells among 31 tissue types during an average individual’s lifetime.  They note that some cancers, such as breast and prostate cancer, were not included in the report because of their inability to find reliable stem cell division rates in the scientific literature.

They hope that other scientists will help refine their statistical model by finding more precise stem cell division rates.

Image courtesy of C. Tomasetti, B. Vogelstein, and Elizabeth Cook (illustrator).

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DOI: 10.1126/science.1260825