Page 160 - 20dynamics of cancer

GENETICS OF PROGRESSION 145

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Figure 8.1 Incidence of unilateral and bilateral retinoblastoma. Redrawn from
Knudson (1971).

Knudson (1971) gave various theoretical justifications for why inher-
ited and sporadic forms should follow these simple models of incidence,
2
proportional either to t for one hit or t for two hits. However, his the-
oretical arguments in that paper ignored the way in which the retina
actually develops. In a later pair of papers, Knudson and his colleagues
produced a theory of incidence that accounts for retinal development
(Knudson et al. 1975; Hethcote and Knudson 1978).
Consider, for example, an individual who inherits one mutation. All
dividing cells in the retina that are at risk for transformation can be
transformed by a single additional somatic mutation. As the retina
grows, the number of cells at risk for a somatic mutation increases,
causing a rise in risk with age. However, the retina grows to near its