Impact of Interleukin-6 –174 G>C Gene Promoter Polymorphism on NeuroblastomaReportar como inadecuado




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Background

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.

Result

To evaluate the impact of IL-6 SNP rs1800795 on disease risk and phenotype, we analyzed 326 Italian NB patients and 511 controls. Moreover, we performed in silico 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 IL-6 gene expression and patient survival. We found that IL-6 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 in silico p = 2.61×10−5 and qRT-PCR p = 0.03 analyses showed similar trend indicating that the CC genotype is correlated with increased level of IL-6 expression. In report gene assay, we showed that the −174 C variant had a significantly increased transcriptional activity compared with G allele p = 0.0006. Moreover, Kaplan-Meier analysis demonstrated that high levels of IL-6 are associated with poor outcome in children with NB in two independent gene expression array datasets.

Conclusions

The biological effect of SNP IL-6–174 G>C in relation to promotion of cancer progression is consistent with the observed decreased survival time. The present study suggests that SNP IL-6–174 G>C may be a useful marker for NB prognosis.



Autor: Francesca Totaro, Flora Cimmino, Piero Pignataro, Giovanni Acierno, Marilena De Mariano, Luca Longo, Gian Paolo Tonini, Achille I

Fuente: http://plos.srce.hr/



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