血管内皮细胞生长抑制因子单核苷酸多态与儿童神经母细胞瘤恶性程度发展的关系

摘要

目的 探讨血管内皮细胞生长抑制因子(VEGI)基因启动子区的单核苷酸多态(SNP)与儿童神经母细胞瘤恶性程度发展的关系.方法 采用病例对照研究方法,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测126例神经母细胞瘤患儿和196例健康儿童VEGI基因启动子区域-358T＞C、-638A＞G多态,Logistic回归模型比较比值比(OR)及95％可信区间(CI)分析上述多态与儿童神经母细胞瘤发展、转移的风险关系.结果 相较于神经母细胞瘤Ⅰ期-358TT野生型,携带VEGI-358CC基因型患儿容易发生肿瘤转移(Ⅱ期,OR=10.667,95％ CI1.387 ～ 82.033,P =0.023;Ⅲ期,OR=5.333,95％ CI0.968 ～ 29.393,P=0.055;Ⅳ期,OR =4.606,95％ CI1.007 ～ 21.072,P=0.049),VEGI-358C等位基因在肿瘤转移过程可能发挥重要作用.携带VEGI-638 GG基因型的患儿相较于野生型AA基因型更易发生肿瘤转移,与VEGI-358位点结果一致,-638G碱基在肿瘤转移过程中发挥重要作用.结论 VEGI-358 T＞C和-638 A＞G多态与儿童神经母细胞瘤发展及转移相关.携带VEGI-358 CC基因型及-638 GG基因型患儿肿瘤侵袭力更强,更易发生转移.%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 (Ⅱ stage,OR =10.667,95 ％ CI 1.387-82.033,P =0.023 ; Ⅲ stage,OR =5.333,95％ CI 0.968-29.393,P =0.055 ; Ⅳ stage,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.