Abstract

Mutations seem to be only one of the mechanisms involved in carcinogenesis; selection of mutated clones is a second crucial mechanism. An evolutionary (darwinian) theory of carcinogenesis can be useful to explain some contradictory observations of epidemiology, and to provide a common theoretical framework for carcinogenesis. In both the selection of species and in carcinogenesis (selection of mutated cells), mutation and selection can be interpreted as necessary and insufficient causes. Selection presupposes competition among clones—that is, survival advantage of the mutated species; without selective forces a mutation is mute, while the lack of mutations makes selective advantage impossible. The identification of carcinogen related fingerprints is ambiguous: it can suggest both a genuine mutational hotspot left by the carcinogenic stimulus (like in tobacco related p53 mutations), and selective advantage of clones whose mutations seem to be not exposure specific (like in the case of aflatoxin). We present several examples of exposures that can increase the risk of cancer in humans not via mutations but through a putative mechanism of clone selection.