Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor).
OBJECTIVE
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.


METHODS
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.
Lagmay
Joanne P
JP
Center for Childhood Cancer, Nationwide Children's Research Institute, The Ohio State University, Columbus, Ohio, USA. lagmayj@gmail.com
London
Wendy B
WB
Gross
Thomas G
TG
Termuhlen
Amanda
A
Sullivan
Nicholas
N
Axel
Amy
A
Mundy
Bethany
B
Ranalli
Mark
M
Canner
Jason
J
McGrady
Patrick
P
Hall
Brett
B
D014408:Biomarkers, Tumor / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D009423:Nervous System Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6