TY - JOUR
T1 - Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma
T2 - rs1800795 (promoter) and rs8192284 (receptor)
AU - Lagmay, Joanne P.
AU - London, Wendy B.
AU - Gross, Thomas G.
AU - Termuhlen, Amanda
AU - Sullivan, Nicholas
AU - Axel, Amy
AU - Mundy, Bethany
AU - Ranalli, Mark
AU - Canner, Jason
AU - McGrady, Patrick
AU - Hall, Brett
PY - 2009/8/15
Y1 - 2009/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=69349093877&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69349093877&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-2953
DO - 10.1158/1078-0432.CCR-08-2953
M3 - Article
C2 - 19671870
AN - SCOPUS:69349093877
SN - 1078-0432
VL - 15
SP - 5234
EP - 5239
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -
