[Genetics and epidemiology of retinoblastoma]

Recent studies of genetic epidemiology of retinoblastoma are reviewed, and major conclusions drawn are as follows: Retinoblastoma occurs in heritable or nonheritable form. The primary genetic change in the heritable form is a point mutation or deletion at a locus on 13 q 14. For the genesis of a tumor in either form, the loss or inactivation of both alleles at this locus is a prerequisite, although additional events may be needed for its development. Information about environmental risk factors for the occurrence of heritable or nonheritable retinoblastoma is still meager. Although viral etiology for nonheritable tumor cannot be excluded, an extensive epidemiologic study revealed no seasonal variation in the births of 675 patients with sporadic unilateral cases, a great majority of which may be regarded as due to somatic mutation. Moreover, there was no paternal age effect at all on the occurrence of 225 sporadic bilateral cases. Paternal exposure to ionizing radiation or chemical mutagens, which should have an accumulated effect with advancing age, does not seem to play a major role in the production of germinal mutation at the Rb locus. Family studies show that host resistance genes at other loci can modify the process of tumor development when the primary genetic change is already present in all the target cells. Unaffected gene carriers may be regarded as inherently resistant to tumor formation, whereas persons who present early onset of bilateral tumors are the most susceptible. In certain families, however, non-expression in the carriers may be due to chromosomal rearrangement in a balanced state.