Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor)
| Autor: | Bethany L. Mundy, Brett Hall, Jason Canner, Nicholas J. Sullivan, Amy Axel, Mark Ranalli, Wendy B. London, Patrick McGrady, Joanne Lagmay, Thomas G. Gross, Amanda Termuhlen |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research Genotype Nervous System Neoplasms Single-nucleotide polymorphism Polymorphism Single Nucleotide Article Neuroblastoma Gene Frequency Predictive Value of Tests Risk Factors medicine Biomarkers Tumor SNP Humans Genetic Predisposition to Disease Interleukin 6 Promoter Regions Genetic Survival analysis biology Interleukin-6 Infant Newborn Interleukin Cancer Infant medicine.disease Prognosis Receptors Interleukin-6 Survival Analysis Oncology Child Preschool Immunology biology.protein Cancer research Female |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 15(16) |
| ISSN: | 1557-3265 |
| Popis: | 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. (Clin Cancer Res 2009;15(16):5234–9) |
| Databáze: | OpenAIRE |
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