An evolutionary perspective on parasitism as a cause of cancer

For the past half-century, the dominant paradigm of oncogenesis has been mutational changes that disregulate cellular control of proliferation. Parasitic causes of cancer were first incorporated into this paradigm by suggesting mechanisms through which parasitism might increase mutational damage, such as generation of mutagenic compounds during immunological activity. The growing recognition of the molecular mechanisms of pathogen-induced oncogenesis and the difficulty of generating oncogenic mutations without first having large populations of dysregulated cells, however, suggests that pathogens, particularly viruses, are major initiators of oncogenesis for many if not most cancers, and that the traditional mutation-driven process becomes the dominant process after this initiation. Molecular phylogenies of individual cancers should facilitate testing of this idea and the identification of causal pathogens.