title: Some GCR Polymorphisms (N363S, ER22/23EK, and Bcl-1) May Influence Steroid-induced Toxicities and Survival Rates in Children With ALL.
abstract: 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.
authors.affiliation: *2nd Department of Paediatrics †United St István and St. László Hospital, Budapest, Hungary.
authors.forename: Oliver
authors.initials: O
authors.lastname: Eipel
authors.forename: Márta
authors.initials: M
authors.lastname: Hegyi
authors.forename: Katalin
authors.initials: K
authors.lastname: Csordás
authors.forename: Krisztina
authors.initials: K
authors.lastname: Németh
authors.forename: Andrea
authors.initials: A
authors.lastname: Luczay
authors.forename: Dóra
authors.initials: D
authors.lastname: Török
authors.forename: Monika
authors.initials: M
authors.lastname: Csóka
authors.forename: Dániel
authors.initials: D
authors.lastname: Erdélyi
authors.forename: Gábor
authors.initials: G
authors.lastname: Kovács
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019938:Cyclin D1 / Q000235:genetics; D018572:Disease-Free Survival; D005938:Glucocorticoids / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007223:Infant; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011241:Prednisone / Q000627:therapeutic use / Q000633:toxicity; D011379:Prognosis; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D013256:Steroids / Q000627:therapeutic use / Q000633:toxicity*; D015996:Survival Rate
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D013256:Steroids; D019938:Cyclin D1; D011241:Prednisone