Hereditary retinoblastoma: host resistance and age at onset

Abstract

Age-specific incidence data from 244 bilateral and 31 familial unlateral cases of retinoblastoma were analyzed. In the bilateral cases, a high intraclass correlation between ages of the patients at diagnosis in the right and left eyes was noted, even after removal of the bias due to the fact that the diagnosis for each eye is never independent. This finding indicated strongly that the age at onset was largely determined by host factors common to both eyes. The mean ages of the patients at diagnosis of the inherited cases among the bilateral or unilateral group varied consistently with parental phenotype. This finding implied that inherited host resistance played an important role in the latency period for the gene carriers. The fraction of cases not yet diagnosed fit well to a negative exponential distribution, and in the less susceptible group with hereditary unilateral cases, tumor formation may have been suppressed about twice that in the most susceptible group with bilateral cases. It was argued that the presumed second hit initiating tumor formation in the gene carriers was not a mutational process, but probably an error in the process of differentiation that could be suppressed completely in the most resistant group who could remain unaffected, but that could not be suppressed completely in the less resistant group.