PURPOSE: Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high-risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival (OS) rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin (IL)-6 and more aggressive behavior in neuroblastoma tumor cells. Therefore, we examined the impact of two IL-6 single nucleotide polymorphisms (SNP) on neuroblastoma disease progression. EXPERIMENTAL DESIGN: DNA samples from 96 high-risk neuroblastoma patients were screened for two SNP that are known to regulate the serum levels of IL-6 and the soluble IL-6 receptor, rs1800795 and rs8192284, respectively. The genotype for each SNP was determined in a blinded fashion and independent statistical analysis was done to determine SNP-related event-free survival (EFS) and OS rates. RESULTS: The rs1800795 IL-6 promoter SNP is an independent prognostic factor for EFS and OS in high-risk neuroblastoma patients. In contrast, the rs8192284 IL-6 receptor SNP revealed no prognostic value. CONCLUSIONS: The rs1800795 SNP [-174 IL-6 (G > C)] represents a novel and independent prognostic marker for both EFS and OS in high-risk neuroblastoma. Because the rs1800795 SNP [-174 IL-6 (G > C)] has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma.
PURPOSE:Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high-risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival (OS) rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin (IL)-6 and more aggressive behavior in neuroblastoma tumor cells. Therefore, we examined the impact of two IL-6 single nucleotide polymorphisms (SNP) on neuroblastoma disease progression. EXPERIMENTAL DESIGN: DNA samples from 96 high-risk neuroblastomapatients were screened for two SNP that are known to regulate the serum levels of IL-6 and the soluble IL-6 receptor, rs1800795 and rs8192284, respectively. The genotype for each SNP was determined in a blinded fashion and independent statistical analysis was done to determine SNP-related event-free survival (EFS) and OS rates. RESULTS: The rs1800795IL-6 promoter SNP is an independent prognostic factor for EFS and OS in high-risk neuroblastomapatients. In contrast, the rs8192284IL-6 receptor SNP revealed no prognostic value. CONCLUSIONS: The rs1800795 SNP [-174 IL-6 (G > C)] represents a novel and independent prognostic marker for both EFS and OS in high-risk neuroblastoma. Because the rs1800795 SNP [-174 IL-6 (G > C)] has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma.
Authors: A Kate Sasser; Bethany L Mundy; Kristen M Smith; Adam W Studebaker; Amy E Axel; Amanda M Haidet; Soledad A Fernandez; Brett M Hall Journal: Cancer Lett Date: 2007-04-27 Impact factor: 8.679
Authors: Peter M Voorhees; Qing Chen; Deborah J Kuhn; George W Small; Sally A Hunsucker; John S Strader; Robert E Corringham; Mohamed H Zaki; Jeffrey A Nemeth; Robert Z Orlowski Journal: Clin Cancer Res Date: 2007-11-01 Impact factor: 12.531
Authors: Brittany J Poelaert; Svetlana Romanova; Shelby M Knoche; Madeline T Olson; Bailee H Sliker; Kaitlin Smits; Brittney L Dickey; Alexandra E J Moffitt-Holida; Benjamin T Goetz; Nuzhat Khan; Lynette Smith; Hamid Band; Aaron M Mohs; Donald W Coulter; Tatiana K Bronich; Joyce C Solheim Journal: J Control Release Date: 2020-07-22 Impact factor: 9.776
Authors: Francesca Totaro; Flora Cimmino; Piero Pignataro; Giovanni Acierno; Marilena De Mariano; Luca Longo; Gian Paolo Tonini; Achille Iolascon; Mario Capasso Journal: PLoS One Date: 2013-10-21 Impact factor: 3.240
Authors: Chike O Abana; Brian S Bingham; Ju Hwan Cho; Amy J Graves; Tatsuki Koyama; Robert T Pilarski; A Bapsi Chakravarthy; Fen Xia Journal: PLoS One Date: 2017-07-21 Impact factor: 3.240