Two-thirds of cancer cases are “bad luck,” study says

Chuck Bednar for – Your Universe Online

Two-thirds of all adult cancer cases are primarily the result of “bad luck,” according to the authors of a new study appearing in Friday’s edition of the journal Science.

Dr. Bert Vogelstein, the Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, and Dr. Cristian Tomasetti, an assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, developed a statistical model that measured the proportion of cancer incidence across many different tissue types.

They found that two-thirds of adult cancer incidence across tissues occur when the random mutations that take place during stem cell division drive cancer through, while the remaining one-third of cases are the result of environmental factors and inherited genes.

“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,” explained Dr. Vogelstein, who is also co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

“Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their ‘good genes,’ but the truth is that most of them simply had good luck,” he said, adding that that poor lifestyle choices can also contribute to this so-called bad luck factor.

The authors said that the implications of their model could alter the public perception about cancer risk factors, as well as impact the funding of research related to the disease.

If most cancer cases can be explained by random DNA mutations that occur as stem cells divide, explained Dr. Tomasetti, it means that lifestyle changes will be a tremendous help when it comes to preventing some forms of the disease, but will be less effective against other types.

As a result, the medical community should “should focus more resources on finding ways to detect such cancers at early, curable stages,” he added. He and Vogelstein said that they reached their conclusion by searching scientific literature for data on the cumulative number of total stem cell divisions among 31 tissue types that take place during a person’s lifetime.

Stem cells renew themselves, repopulating cells that die off in specific organs, the researchers said. Cancer arises when tissue-specific stem cells experience mutations in which one chemical letter in DNA is erroneously swapped for another during the replication process.

As more of these mutations accumulate, the risk that cells will grow unchecked (a hallmark of cancer) increases. However, the actual amount that these random mistakes contribute to cancer incidence in comparison to hereditary or environmental factors was previous unknown.

To figure out what role these mutations play, the researchers charted the number of stem cell division in 31 tissues and compared those rates to the lifetime risks of cancer in the same tissues in American adults. They determined that there was a 0.804 correlation between the number of the total number of stem cell divisions and cancer risk, meaning they are linked.

“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 said. For instance, colon tissue undergoes four times more stem cell divisions than small intestine tissue in humans, and as a result, colon cancer is far more prevalent than small intestinal cancer.

While Tomasetti said that a person “could argue that the colon is exposed to more environmental factors than the small intestine, which increases the potential rate of acquired mutations,” he and his colleague found that the opposite was actually true in mice.

They had a lower number of stem cell divisions in their colons than in their small intestines, and cancer incidence is lower in the colon than it is in the small intestine. This discovery, the authors said, supports the role of the total number of stem cell divisions in cancer development.

They went on to statistically calculate which cancer types had an incidence predicted by the number of stem cell divisions and which had higher incidence, and found that there were 22 types that could be primarily explained by random DNA mutations during cell divisions, while the other nine were believed to be due to a combination of all three 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 said.

“This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors,” he added. “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 authors also noted that some types of cancers, including breast and prostate cancer, were not included in the report because they were unable to find reliable stem cell division rates for those diseases in scientific literature. They hope that other researchers will help refine their statistical model by locating more precise stem cell division rates.


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