Scientists from the Johns Hopkins Kimmel Cancer Center have created a statistical model that measures the proportion of cancer incidence, across many tissue types, caused mainly by random mutations that occur when stem cells divide. By their measure, two-thirds of adult cancer incidence across tissues can be explained primarily by “bad luck,” when these random mutations occur in genes that can drive cancer growth, while the remaining third are due to environmental factors and inherited genes.
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.
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.
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