Evaluating the Effect of 3 Glucocorticoid Receptor Gene Polymorphisms on Risk of Relapse in 100 Iranian Children With Acute Lymphoblastic Leukemia: A Case-Control Study

• Published in: Clinical therapeutics Vol. 33; no. 3; pp. 280 - 290
• Main Authors: Namazi, Soha, PharmD, PhD, Zareifar, Soheila, MD, Monabati, Ahmad, MD, Ansari, Shahla, MD, Karimzadeh, Iman, PharmD
• Format: Journal Article
• Language: English
• Published: Bridgewater, NJ EM Inc USA 01.03.2011; Elsevier; Elsevier Limited
• Subjects: acute lymphoblastic leukemia; Adolescent; Biological and medical sciences; Body mass index; Bone density; Case-Control Studies; Cell cycle; Chemotherapy; Child; Child, Preschool; childhood; Children & youth; DNA - genetics; Drug therapy; Female; Gene Frequency; Genetic Association Studies; Genotype; glucocorticoid receptor gene; Hematologic and hematopoietic diseases; Humans; Infant; Internal Medicine; Iran - epidemiology; Iranian population; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical Education; Medical prognosis; Medical sciences; Pharmacology. Drug treatments; Polymerase Chain Reaction; polymorphism; Polymorphism, Restriction Fragment Length; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Receptors, Glucocorticoid - genetics; Recurrence; relapse; Iran; Asia; polymorphism; Iranian population; childhood; acute lymphoblastic leukemia; relapse; glucocorticoid receptor gene; Human; Relapse; Genetic variability; Genotype; Malignant hemopathy; Case control study; Gene; Lymphoproliferative syndrome; Risk factor; Glucocorticoid receptor; Genetics; Acute lymphocytic leukemia; Child; Cancer; Polymorphism; Hormonal receptor
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2011.03.004

Abstract Background Glucocorticoids are an important component of treatment for childhood acute lymphoblastic leukemia (ALL). To induce antileukemic effects, glucocorticoids have to bind their intracellular receptors. Little is known about probable mechanisms of glucocorticoid resistance in ALL. Objective The aim of this study was to evaluate the possible association between 3 prominent glucocorticoid receptor gene polymorphisms— Bcl I, N363S, and ER22/23EK—and the risk of relapse in children with ALL. Methods We conducted a case-control study on 100 children with ALL, aged 0 to 15 years, including 50 nonrelapsed (control) and 50 relapsed (case) subjects. Required patient information such as demographic characteristics; relevant clinical and paraclinical findings at diagnosis; chemotherapy protocols used at diagnosis; and relapse properties, including time interval from date of initial diagnosis to relapse and number, type, and site of relapse, were gathered from patients' medical files. Genotyping of Bcl I, N363S, and ER22/23EK polymorphisms was carried out by polymerase chain reaction restriction fragment–length polymorphism (PCR–RFLP). Statistical analysis was performed. The distribution of Bcl I, N363S, and ER22/23EK polymorphism genotypes in our population and in populations examined in similar studies was compared using the χ2 test or Fischer exact test. Results One hundred children with ALL, consisting of 65 males and 35 females, were recruited into this study. Their mean (SD) age was 5.39 (3.02) years. No relapsed or nonrelapsed individuals were homozygous for N363S and ER22/23EK polymorphisms. The allelic frequencies of mutant alleles of Bcl I, N363S, and ER22/23EK polymorphisms in all patients were 0.195, 0.02, and 0.005, respectively. No statistically significant association between Bcl I, N363S, and ER22/23EK polymorphisms and risk of relapse in children with ALL was observed ( P = 0.104 [ Bcl I], not calculated for the last 2 polymorphisms [N363S and ER22/23EK]). The incidence of Bcl I polymorphism in our population (35/100) differed significantly from that in a Canadian population with European descent (135/219) and a Dutch population (29/53) ( P < 0.001 and P = 0.007, respectively). Conclusion Our data suggest that there did not appear to be any prognostic value of Bcl I, ER22/23EK, and N363S polymorphisms for predicting relapse in this population of 100 Iranian children with ALL.