Math Suggests Most Cancers Are Caused By "Bad Luck"

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Two-thirds of all cancers are caused by random mutations and not genetics or lifestyle factors, say scientists from Johns Hopkins University in Baltimore, MD.

The new paper, which now appears in the journal Science, suggests that 22 out of the 31 cancer types analyzed are simply the result of biological bad luck. These include leukemia, pancreatic, bone, testicular, brain, and ovarian cancers. Writing in Science AAAS, Jennifer Couzin-Frankel explains how the researchers came to this conclusion:

Here's how it works: Take the number of cells in an organ, identify what percentage of them are long-lived stem cells, and determine how many times the stem cells divide. With every division, there's a risk of a cancer-causing mutation in a daughter cell. Thus, [Cristian] Tomasetti and [Bert] Vogelstein reasoned, the tissues that host the greatest number of stem cell divisions are those most vulnerable to cancer. When Tomasetti crunched the numbers and compared them with actual cancer statistics, he concluded that this theory explained two-thirds of all cancers.

"Using the mathematics of evolution, you can really develop an engineerlike understanding of the disease," says Martin Nowak, who studies mathematics and biology at Harvard University and has worked with Tomasetti and Vogelstein. "It's a baseline risk of being an animal that has cells that need to divide."

The idea emerged during one of the pair's weekly brainstorming sessions in Vogelstein's office. They returned to an age-old question: How much of cancer is driven by environmental factors, and how much by genetics? To solve that, Tomasetti reasoned, "I first need to understand how much is by chance and take that out of the picture."


When the scientists say it's a matter of "chance," they're talking about the odds of random DNA mutations accumulating in various parts of the body during ordinary cell division, while excluding the influence of heredity or environmental factors such as smoking.

Take colon cancer, for example, which is far more common than cancer of the duodenum. The researchers found that there are about about 1012 stem cell divisions in the colon over a lifetime, compared with 1010 in the duodenum. This would explain why certain tissue types give rise to cancers millions of times more often that other tissue types. As the researchers note in their paper, "[The] lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis."


In all, the researchers found that 65% of cancer incidence can be attributed to random mutations in genes that drive cancer growth.

Now that said, there are certain types of cancers that are most definitely influenced by genetics and lifestyle factors. Of the nine types of cancer not attributed to "back luck," the researchers identified such conditions as colorectal cancer, basal cell carcinoma (a kind of skin cancer), and smoking-related cancer. This research suggests that we should adjust our lifestyles to prevent the onset of certain cancers, but that some cancers are simply beyond our control.


More at Science AAAS.

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