Do mutations cause cancer? (or the dog that did not bark)

Evolution is change over time, and it is well-accepted that cancers evolve through the stepwise accumulation of somatic mutations. Logically, mutations ‘cause’ cancer, and therefore, simplistically, the key to preventing cancer could be to avoid mutations. However, epithelium, like the skin and intestines, divide and shed millions of cells every day, and could accumulate many mutations because DNA replication is imperfect.

One potential safeguard against ‘replication’ errors is a stem cell hierarchy, where long-lived stem cells divide infrequently. However, studies in mice indicate that both skin¹ and intestinal stem cells² are not quiescent but rather are actively dividing. Such tissues are primed for evolution because many more cells are produced than can survive.