జర్నల్ ఆఫ్ కార్సినోజెనిసిస్ & మ్యూటాజెనిసిస్

నైరూప్య

A New Stochastic Model of Retinoblastoma Involving both Hereditary and Non-hereditary Cancer Cases

Wai-Yuan Tan and Hong Zhou

Background and purpose: Retinoblastoma is initiated by the mutation or loss or inactivation of the retinoblastoma gene (the Rb gene) in chromosome 13q14. Further, both the germline cells (eggs and sperm) generating the individuals may carry a mutant allele of the Rb gene so that individuals may carry both mutants in the Rb locus at the embryo stage in which case cancer tumor may develop at or before birth. Recent molecular studies have also shown that besides the abrogation of cell dierentiation by the inactivation of the Rb locus, the apoptosis mechanism needs also to be inhibited or abrogated for the generation of retinoblastoma tumor. The purpose of this paper is to develop new stochastic and statistical models for retinoblastoma to incorporate these biological findings.

Results: Based on recent biological studies, in this paper we have developed a discrete-time stochastic multistage model and a generalized mixture model for retinoblastoma to account for hereditary cancer cases. We have applied this model to fit and analyze the SEER data of retinoblastoma from NCI/NIH. Our results indicate that a modified MVK (Moolgavkar-Venzon-Knudson) two-stage model with discrete time fits the data much extremely well and better than a three-stage model.

Conclusion: Our studies have shown that retinoblastoma can best be described by a modified MVK two-stage model with discrete time. It appears that this new model would not only provide more insights into retinoblastoma but also would provide useful guidance for its prevention and control and for prediction of future cancer cases.