In order to assess the role of genetic predisposition in the induction of 
radiation-induced tumors, we performed statistical analysis on data from the 
literature and from our own Institute with regard to the age at onset and the 
latency period of osteosarcoma as the second primary tumor for retinoblastoma 
with or without subsequent radiotherapy. In retinoblastoma survivors who 
subsequently developed osteosarcoma, the age at onset of retinoblastoma was 
young (average of 12 months) in both unilateral and bilateral forms. This 
suggests that all or almost all of the patients were genetically predisposed by 
a mutation of one allele of the RB1 gene. For retinoblastoma patients, 
osteosarcomas occurred 1.2 years earlier inside than outside the radiation 
field. The latency period between radiotherapy and osteosarcoma onset was 1.3 
years shorter inside than outside the radiation field. Interestingly, a bimodal 
distribution of latency periods was observed for osteosarcomas arising inside, 
but not outside the radiation field: 40% occurred after a short latency, while 
the latency of the remaining 60% was comparable to that of osteosarcoma 
occurring outside the radiation field. This suggests that different mechanisms 
may be involved in radiocarcinogenesis. A radiation-induced mutation of the 
second RB1 allele may be the cause of osteosarcomas occurring after a short 
delay, while other genes may be affected in those occurring after a longer 
delay.