<div><p>Background</p><p>Common variants in DNA may predispose to onset and progression of neuroblastoma (NB). The genotype GG of single nucleotide polymorphism (SNP) rs1800795 (−174 G>C) in interleukin (IL)-6 promoter has been associated with lower survival of high-risk NB.</p><p>Result</p><p>To evaluate the impact of <i>IL-6</i> SNP rs1800795 on disease risk and phenotype, we analyzed 326 Italian NB patients and 511 controls. Moreover, we performed <i>in silico</i> and quantitative Real Time (qRT)-PCR analyses to evaluate the influence of the SNP on gene expression in 198 lymphoblastoid cell lines (LCLs) and in 31 NB tumors, respectively. Kaplan-Meier analysis was used to verify the association between <i>IL-6</i> gene expression and patient survival. We found that <i>IL-6</i> SNP is not involved in susceptibility to NB development. However, our results show that a low frequency of genotype CC is significantly associated with a low overall survival, advanced stage, and high-risk phenotype. The <i>in silico</i> (<i>p</i> = 2.61×10<sup>−5</sup>) and qRT-PCR (<i>p</i> = 0.03) analyses showed similar trend indicating that the CC genotype is correlated with increased level of <i>IL-6</i> expression. In report gene assay, we showed that the −174 C variant had a significantly increased transcriptional activity compared with G allele (<i>p</i> = 0.0006). Moreover, Kaplan-Meier analysis demonstrated that high levels of <i>IL-6</i> are associated with poor outcome in children with NB in two independent gene expression array datasets.</p><p>Conclusions</p><p>The biological effect of SNP <i>IL-6</i>–174 G>C in relation to promotion of cancer progression is consistent with the observed decreased survival time. The present study suggests that SNP <i>IL-6</i>–174 G>C may be a useful marker for NB prognosis.</p></div
