Aurora-A遗传变异Phe31Ile与小儿神经母细胞瘤遗传易感性

目的Aurora-A基因过度表达可引起中心粒异常、染色体不稳定和肿瘤形成。本研究探讨Aurora-APhe31Ile多态与神经母细胞瘤（neuroblastoma,NB）遗传易感性的关系。方法以聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析方法,检测了19例NB病人和144例正常对照者Aurora-APhe31Ile基因型,比较不同基因型与NB发生和发展的关系。结果Aurora-AIle等位基因频率在NB患者和正常对照中的分布有显著性差异（76.3%vs.49.0%,P=0.04）。Aurora-A三种基因型Phe/Phe、Phe/Ile和Ile/Ile在病例和对照组中的分布有统计学显著性差异（P=0.05,趋势检验）,携带Aurora-AIle/Ile基因型者罹患NB的风险是Phe/Phe或Phe/Ile基因型携带者的2.51倍（95%CI,0.86-7.37）。结论Aurora-A遗传变异Phe31Ile可能是我国神经母细胞瘤的遗传易感因素。

Role of Aurora-A Phe31 Ile polymorphism in the genetic susceptibility of neuroblastoma

Objective：Aurora-A is involved in regulating centrosomes and chromosome segregation.The Phe31Ile polymorphism in Aurora-A alters the kinase function,with the Ile variant being preferentially amplified and associated with degree of aneuploidy in human tumors.This case-control study examined the contribution of this polymorphism to susceptibility of neuroblastoma.Methods：Genotypes were determined in 19 patients with neuroblastoma and 144 normal controls.The odds ratios（ORs） and 95% confidence intervals（CIs） were calculated using logistic regression model.Results：We found that the frequency of the Aurora-A Ile allele was significantly higher in cases than in controls（76.3% vs.49.0%,P = 0.04）.The difference among distribution of three genotypes Phe/Phe,Phe/Ile and Ile/Ile was statistically significant between cases and controls（P = 0.05,trend test）.Subjects with the Ile/Ile genotype had an increased risk for the occurrence of NB compared with those with the Phe/Phe or Phe/Ile genotypes with borderline significance.Conclusion：These findings suggest that Aurora-A Phe31Ile variation may be a genetic susceptibility factor for neuroblastoma in Chinese population.