Association Between N363S and BclI Polymorphisms of the Glucocorticoid Receptor Gene (NR3C1) and Glucocorticoid Side Effects During Childhood Acute Lymphoblastic Leukemia Treatment.
OBJECTIVE
Glucocorticoids (GCs) are the key drugs for the treatment of pediatric acute lymphoblastic leukemia (ALL). Herein, investigation of the relationship between the N363S and BclI polymorphisms of the GC receptor gene (NR3C1) and the side effects of GCs during pediatric ALL therapy was aimed.


METHODS
N363S and BclI polymorphisms were analyzed in 49 patients with ALL treated between 2000 and 2012. The control group consisted of 46 patients with benign disorders. The side effects of GCs noted during the induction and reinduction periods were evaluated retrospectively according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0.


RESULTS
The BclI allele and genotype frequencies were found similar in the two groups. No N363S polymorphism was detected in either of the groups. During induction, dyspepsia was found more frequently in the 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). During reinduction, Cushingoid changes, dyspepsia, and depression symptoms were more frequent in patients with the G allele (CG+GG) than in patients 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).


CONCLUSIONS
In our study, patients with the BclI polymorphism were found to have developed more frequent side effects. We think that the BclI polymorphism should be considered while designing individualized therapies in childhood ALL.
Meriç
M
Kaymak Cihan
Halil Gürhan
HG
Karabulut
Nüket
N
Yürür Kutlay
Hatice
H
Ilgın Ruhi
Ajlan
A
Tükün
Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Clinic of Pediatrics, Division of Pediatric Hematology-Oncology, Ankara, Turkey Phone: +90 532 760 09 82 E-mail: laleolcay@hotmail.com.tr.
Lale
L
Olcay
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012189:Retrospective Studies
D005938:Glucocorticoids; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid