Cancer genesis across the age spectrum: associations with tissue development, maintenance, and senescence

Cancer genesis across the age spectrum is a complex, multifactorial process, and parallels changes in site-specific tissue development, maintenance, and senescence. Cancer is not a single disease, and different tumor and stem cells may demonstrate various manifestations of abnormal function. Mutations in DNA, some random and some explained by exogenous insults, accompanied by changes in the tissue microenvironment, generally precede the onset of aberrant replication and apoptosis. Moreover, increasing evidence suggests that genetic programs normally active only during development of human beings may be reactivated during tumorigenesis. The complicated underlying biology of human growth, development, and carcinogenesis is reflected in the highly disparate patterns in site-specific cancer incidence rates across age groups. In childhood, the peak years of an organ system's increase in size correlate with peak years of cancer incidence. Conversely, in most adult-onset cancers, it is exposure to exogenous toxins, the failure of maintenance and repair, and finally, dysfunction(s) in the normal cellular aging process that likely play a role in the development of these malignancies. Additional basic science investigations and epidemiologic studies will assist in our understanding of the mechanisms that underlie the notable difference in site-specific cancer incidence according to age.