Genetic, epigenetic, dysgenetic, and non-genetic mechanisms in tumorigenesis

A not yet understood phenomenon in carcinogenesis is the enormous difference in cancer susceptibility of cells from different species and of cells from individuals within the same species but with different age. Reviewing of the literature points to the promotion phase as the key for this difference. The essence of promotion appears to be a profound switch in the cell functions that enable cells to respond to stresses such as those caused by wounds and infection (cell activation). It was suggested that this switch involves an increase in the life span of the cells which, in turn, may predispose them to immortalization. A relationship of this switch with the onset of genetic instability was suggested, but it is not clear whether genetic instability is inherent to this switch or due to an incorrect performance of either switching on or switching off the response. The cause of species and age-specific differences in cancer susceptibility has therefore been sought in species and age-specific differences on the regulatory control of cell activation, an area that is still largely a black box.