Some GCR Polymorphisms (N363S, ER22/23EK, and Bcl-1) May Influence Steroid-induced Toxicities and Survival Rates in Children With ALL
| Autor: | Dóra Török, Olivér Eipel, Márta Hegyi, Gabor G. Kovacs, Krisztina Németh, Andrea Luczay, Monika Csóka, Katalin Csordás, Dániel J. Erdélyi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Adolescent Single-nucleotide polymorphism Carbohydrate metabolism Gastroenterology Disease-Free Survival 03 medical and health sciences Receptors Glucocorticoid 0302 clinical medicine Glucocorticoid receptor Glucocorticoid Sensitivity Prednisone Internal medicine Genotype medicine Humans SNP Cyclin D1 Child Glucocorticoids Survival rate Polymorphism Genetic business.industry Infant Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Prognosis Survival Rate 030104 developmental biology Oncology Child Preschool 030220 oncology & carcinogenesis Pediatrics Perinatology and Child Health Steroids business medicine.drug |
| Zdroj: | Journal of Pediatric Hematology/Oncology. 38:334-340 |
| ISSN: | 1077-4114 |
| DOI: | 10.1097/mph.0000000000000535 |
| Popis: | We investigated whether an altered individual glucocorticoid sensitivity due to particular glucocorticoid receptor single-nucleotide polymorphisms (SNPs) (N363S, ER22/23EK, and Bcl-1) influences the susceptibility to steroid-related toxicities, prognostic factors, and survival rates in children with acute lymphoblastic leukemia. In total, 346 pediatric patients with acute lymphoblastic leukemia were enrolled in our study. Their carrier status was investigated by allele-specific polymerase chain reaction analysis. Clinical and laboratory signs of glucocorticoid-related toxicities, day-8 prednisone response, 5-year event-free survival, and 5-year overall survival rates were analyzed and compared retrospectively. Hepatotoxicity occurred significantly more often in 363S carriers (P=0.004), and glucose metabolism abnormalities were more common in 363S carriers (P=0.001), but did not occur in patients with the ER22/23EK SNP. Hypertension and central nervous system/behavioral changes did not occur in patients with the ER22/23EK SNP. None of the patients with the N363S SNP, the ER22/23EK polymorphism, or the GG genotype for the Bcl-1 polymorphism had a poor prednisone response. The 363S carriers had significantly better 5-year event-free survival (P=0.012) and 5-year overall survival (P=0.013) rates compared with noncarriers. The Bcl-1 SNP was not associated with any of the toxicities investigated or survival. Children with the N363S polymorphism in the glucocorticoid receptor gene were more prone to steroid-related toxicities, whereas those with the ER22/23EK polymorphism were less susceptible. Children with the N363S polymorphism may have more favorable survival rates. |
| Databáze: | OpenAIRE |
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