In the case of solid tumours, epidemiological evidence indicates that as many as 20 years pass between the time an individual is exposed to a carcinogen to the clinical appearance of a tumour. Various barriers to tumour progression exist, including DNA repair processes, the availability of nutrition, the requirement of angiogenesis to allow the tumour to increase in size and responses to hypoxia. Circles represent mutations in genes that result in enhanced mutagenesis, triangles indicate driver mutations that are selected on the basis of changes in the tumour microenvironment and white rectangles represent passenger mutations.