Analysis of retinoblastoma age incidence data using a fully stochastic cancer model
| Autor: | Guangquan Li, M E Kroll, Ruth A. Kleinerman, Michael F.G. Murphy, Mark P. Little, Charles A. Stiller |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Mutation rate Adolescent Genotype Stochastic modelling Cancer Model Population Biology Article Mutation Rate medicine Humans Genes Retinoblastoma Allele Child education Alleles Genetics education.field_of_study Models Statistical Retinoblastoma Incidence Incidence (epidemiology) Age Factors Infant Newborn Infant medicine.disease eye diseases Oncology Evolutionary biology Child Preschool |
| Zdroj: | International Journal of Cancer. 130:631-640 |
| ISSN: | 0020-7136 |
| Popis: | Retinoblastoma (RB) is an important ocular malignancy of childhood. It has been commonly accepted for some time that knockout of the two alleles of the RB1 gene is the principal molecular target associated with the occurrence of RB. In this paper, we examine the validity of the two-hit theory for retinoblastoma by comparing the fit of a stochastic model with two or more mutational stages. Unlike many such models, our model assumes a fully stochastic stem cell compartment, which is crucial to its behavior. Models are fitted to a population-based dataset comprising 1,553 cases of retinoblastoma for the period 1962–2000 in Great Britain (England, Scotland, Wales). The population incidence of retinoblastoma is best described by a fully stochastic model with two stages, although models with a deterministic stem cell compartment yield equivalent fit; models with three or more stages fit much less well. The results strongly suggest that knockout of the two alleles of the RB1 gene is necessary and may be largely sufficient for the development of retinoblastoma, in support of Knudson’s two-hit hypothesis. |
| Databáze: | OpenAIRE |
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