Association Between N363S and BclI Polymorphisms of the Glucocorticoid Receptor Gene (NR3C1) and Glucocorticoid Side Effects During Childhood Acute Lymphoblastic Leukemia Treatment

摘要

Objective: Glucocorticoids (GCs) are the key drugs for the treatmentof pediatric acute lymphoblastic leukemia (ALL). Herein, investigationof the relationship between the N363S and BclI polymorphisms of theGC receptor gene (NR3C1) and the side effects of GCs during pediatricALL therapy was aimed.Materials and Methods: N363S and BclI polymorphisms wereanalyzed in 49 patients with ALL treated between 2000 and 2012. Thecontrol group consisted of 46 patients with benign disorders. The sideeffects of GCs noted during the induction and reinduction periodswere evaluated retrospectively according to the National CancerInstitute’s Common Terminology Criteria for Adverse Events, version4.0.Results: The BclI allele and genotype frequencies were found similarin the two groups. No N363S polymorphism was detected in either ofthe groups. During induction, dyspepsia was found more frequently inthe CG than in the CC (wild-type) genotype (36.4% vs. 5.3%, p=0.018)and depression symptoms more frequent in patients with the G allele(CG+GG) than the CC genotype (39.3% vs. 10.5%, p=0.031). Duringreinduction, Cushingoid changes, dyspepsia, and depression symptomswere more frequent in patients with the G allele (CG+GG) than inpatients with the CC genotype (48.1% vs. 17.6%, p=0.041; 29.6% vs.0.0%, p=0.016; 40.7% vs. 11.8%, p=0.040, respectively).Conclusion: In our study, patients with the BclI polymorphismwere found to have developed more frequent side effects. We thinkthat the BclI polymorphism should be considered while designingindividualized therapies in childhood ALL.