Ciência e terapia do câncer

Association of Caspase 8 and Caspase 10 Genetic Polymorphisms with B-cell Non Hodgkin's Lymphoma in Egypt: A Case-Control Study

Abstract

Hanaa Hamed Arnaout, Mervat Mamdooh Khorshied, Ola M. Reda Khorshid and Mona Hazem El-Nagdy

Background and purpose: Non-Hodgkin lymphomas are closely related diseases with distinctive morphologic, immunophenotypic, genetic, and clinical features. Genetic susceptibility studies of NHL are mandatory to identify at risk populations and to clarify important disease mechanisms. Caspase genes play a key role in regulation of apoptotic cell death, and dysregulation of this signaling pathway has been shown to participate in tumorigenesis. The current study aimed at defining the role of Caspase 8-D302H, Caspase 8-652 6N ins/del and Caspase 10-I522L genetic polymorphisms as risk factors for NHL and their possible role as genetic prognostic markers.   Methods: The present study included 100 Egyptian B-cell NHL patients and 100 healthy controls. Genotyping of the studied genes was performed by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique. Data was analyzed using SPSS statistical package version 15.   Results: The study revealed that CASP8-D302H mutant genotypes were significantly higher in NHL patients when compared to the controls and conferred increased risk of NHL. For CASP8-652 6N ins/del and Casp10- I522L, there was no statistical difference in the distribution of the different genotypes between NHL cases and the controls. Furthermore, there were no statistical differences between NHL patients harboring the wild or mutant genotypes of the studied genes as regards their response to therapy.   Conclusions: CASP8-D302H genetic polymorphism represents a genetic risk factor for NHL in Egyptian population. Hopefully, better understanding of the functional consequences of caspase genes polymorphism would provide a foundation for future studies of the possible role of these genes in lymphomagenesis.