Abstract
Abstract
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. Here, we show that 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. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.
Editor's Summary
Crunching the numbers to explain cancer
Why do some tissues give rise to cancer
in humans a million times more frequently than others? Tomasetti and
Vogelstein conclude
that these differences can be explained by the
number of stem cell divisions. By plotting the lifetime incidence of
various
cancers against the estimated number of normal
stem cell divisions in the corresponding tissues over a lifetime, they
found
a strong correlation extending over five orders
of magnitude. This suggests that random errors occurring during DNA
replication
in normal stem cells are a major contributing
factor in cancer development. Remarkably, this “bad luck” component
explains
a far greater number of cancers than do
hereditary and environmental factors.
Science/AAAS | News
"...For Vogelstein, one major message is that cancer often cannot be prevented, and more resources should be funneled into catching it in its infancy. “These cancers are going to keep on coming,” he says.
Douglas Lowy, a deputy director of the National Cancer Institute in Bethesda, Maryland, agrees, but also stresses that a great deal of “cancer is preventable” and efforts to avert the disease must continue.
Although the randomness of cancer might be frightening, those in the field see a positive side, too. The new framework stresses that “the average cancer patient … is just unlucky,” Clevers says. “It helps cancer patients to know” that the disease is not their fault."
