Carcinogenesis revisited.

The importance of mutations in carcinogenesis is still unclear. Assuming that mutations of the genetic material are central to this problem, the number needed to give rise to a cancer cell must be established. A one-mutation theory is unsatisfactory for a number of reasons. A four-mutation model fits better and can be calculated in humans assuming that the observed endogenous tumors in 2% of the population equals the frequency of spontaneous carcinogenesis, accepting a mean mutation rate of 2 X 10(-5) mutations per gene per generation, and a production of about 7 X 10(15) cells during our whole lifetime. This model is also consistent with the observed peak incidence of cancer in children, with the hereditary aspects of some pediatric tumors, and with the usually nonhereditary mechanisms of cancer in adults.