Journals / Turkish Journal of Hematology / 2017 / Cilt: 34 - Sayı: 2

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

Glukokortikoid Reseptör Geninin (NR3C1) N363S ve BclI Polimorfizmleri ile Çocukluk Çağı Akut Lenfoblastik Lösemi Tedavisi Sırasında Görülen Glukokortikoid Yan Etkileri Arasındaki İlişki

Pages
151–158
DOI
—
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

We think that the BclI polymorphism should be considered while designing individualized therapies in childhood ALL.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Glucocorticoids (GCs) are the key drugs for the treatment of pediatric acute lymphoblastic leukemia (ALL).
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Key Findings & Data: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.Materials and Methods: N363S and BclI polymorphisms were analyzed in 49 patients with ALL treated between 2000 and 2012.
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Conclusion & Impact:We think that the BclI polymorphism should be considered while designing individualized therapies in childhood ALL.
🔬Design:Research Article
📍Scope:2000 Verileri
⚙️Variables:Domain Parameters

Abstract

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.Materials and 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). Conclusion: 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.

Özet

Amaç: Çocukluk çağı akut lenfoblastik lösemisinde (ALL), glukokortikoidler (GC) tedavinin ana yapı taşını oluşturmaktadırlar. Bu çalışmada pediatrik ALL tedavisi sırasında GC'lerin yan etkileri ile GC reseptör geninin (NR3C1) N363S ve BclI polimorfizmleri arasındaki ilişkinin araştırılması amaçlandı.Gereç ve Yöntemler: N363S ve BclI polimorfizmleri 2000 ile 2012 yılları arasında tedavi edilmiş 49 ALL hastasında incelendi. Kontrol grubu benign hastalıkları olan 46 çocuktan oluşturuldu. İndüksiyon ve reindüksiyon sırasında görülen GC yan etkileri Ulusal Kanser Enstitüsü'nün "Advers Etkiler için Ortak Terminoloji Kriterleri" (CTCAE version 4,0), kullanılarak dosya ve hemşire gözlemlerinden geriye dönük olarak incelendi. Bulgular: BclI alel ve genotip sıklığı açısından iki grup arasında fark yoktu. N363S polimorfizmi her iki grupta da tespit edilmedi. İndüksiyon sırasında, dispeptik yakınmalar CG genotipinde CC (yaban tip) genotipine göre daha sık görüldü (%36,4-%5,3; p=0,018) ve depresyon semptomları G alelini taşıyanlarda (CG+GG), CC genotipine göre daha sık tespit edildi (%39,3-%10,5; p=0,031). Reindüksiyon sırasında, Cushingoid değişiklikler, dispeptik yakınmalar ve depresyon semptomları G aleli taşıyanlarda (CG+GG) CC genotipine göre daha fazla tespit edildi (sırasıyla %48,1-%17,6, p=0,041; %29,6-%0,0 p=0,016; %40,7-%11,8; p=0,040). Sonuç: Çalışmamızda, BclI polimorfizmine sahip bireyler daha sık yan etki gösterdiler. Çocukluk çağı ALL tedavisinde bireysel tedaviler geliştirilirken BclI polimorfizminin de göz önünde bulundurulmasının gerektiğini düşünüyoruz.

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Cite This Article

KAYMAK, M. C., KARABULUT, H. G., YÜRÜR, N. K., RUHİ, H. I., TÜKÜN, A., OLCAY, L. (2017). Association Between N363S and BclI Polymorphisms of the Glucocorticoid Receptor Gene (NR3C1) and Glucocorticoid Side Effects During Childhood Acute Lymphoblastic Leukemia Treatment. Turkish Journal of Hematology, Cilt: 34 - Sayı: 2, 151–158. https://ajindex.com/articles/412460

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