Single nucleotide polymorphisms in vascular endothelial growth inhibitor and its association with development and metastasis of children's neuroblastoma

Abstract

Objective To identify functional single nucleotide polymorphisms(SNPs) in the promoter region of vascular endothelial growth inhibitor(VEGI) gene and to explore the relationship between these SNPs and the development and metastasis of children's neuroblastoma. Methods A case-control study was performed using PCR-restriction fragment length polymorphism(PCR-RFLP) assay in 126 patients with neuroblastoma and 196 healthy children to detect the genotype-358 T>C, -638 A>G of VEGI promoter region.The association between SNPs of VEGI and neuroblastoma in children was analyzed by using Logistic regression model.Odds ratios(OR) and 95% confidence intervals(CI) were estimated by using Logistic regression. Results Two SNPs, VEGI-358T>C and -638A>G located upstream the translation start site were identified associating with Logistic regression analysis showed that subjects carrying the VEGI-358CC and-638GG genotype played an important role of tumor malignancy in children(Ⅱstage, OR=10.667, 95%CI 1.387-82.033, P=0.023; Ⅲstage, OR=5.333, 95%CI 0.968-29.393, P=0.055; Ⅳstage, OR=4.606, 95%CI 1.007-21.072, P=0.049). The VEGI -638GG genotype significantly increased the risk of tumor malignancy in children, and the result was the same as VEGI -358CC. Conclusions These findings indicate that functional genetic variants in VEGI -358T>C and -638A>G may play an important role in neuroblastoma progression in children.VEGI -358CC and -638GG carriers have higher risk of proliferation and metastasis of neuroblastoma. Key words: Neuroblastoma; Vascular endothelial growth inhibitor; Single nucleotide polymorphisms; Metastasis