He Jing, Zou Yan, Liu Xiaodan, Zhu Jinhong, Zhang Jiao, Zhang Ruizhong, Yang Tianyou, Xia Huimin
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Mol Ther Nucleic Acids. 2018 Jun 1;11:1-8. doi: 10.1016/j.omtn.2018.01.003. Epub 2018 Jan 31.
Neuroblastoma is a commonly occurring extracranial pediatric solid tumor without defined etiology. Polymorphisms in pre-miRNAs have been demonstrated to associate with the risk of several cancers. So far, no such polymorphism has been investigated in neuroblastoma. With this in mind, we performed a two-center case-control study to assess the association of genetic variants in pre-miRNAs and neuroblastoma susceptibility in Chinese children, including 393 cases and 812 controls. We found that miR-34b/c rs4938723 T > C polymorphism was significantly associated with decreased neuroblastoma risk (TC versus TT: adjusted odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.39-0.67; TC/CC versus TT: adjusted OR = 0.62, 95% CI = 0.48-0.79). We also observed the significant association between the miR-218 rs11134527 A > G polymorphism and decreased neuroblastoma risk (AG versus AA: adjusted OR = 0.73, 95% CI = 0.56-0.96). Stratified analysis further demonstrated that the protective effect of the rs4938723 T > C polymorphism remained prominent in the subgroups, regardless of age, gender, and clinical stages. In term of sites of origin, this polymorphism significantly reduced the risk of tumors originating from the adrenal gland. We further validated the significant results using false-positive report probability analyses. Overall, the miR-34b/c rs4938723 T > C and miR-218 rs11134527 A > G polymorphisms displayed a protective role from neuroblastoma. These findings need further validation.
神经母细胞瘤是一种常见的儿童颅外实体瘤,病因尚不明确。前体微小RNA(pre-miRNA)的多态性已被证明与多种癌症的风险相关。迄今为止,尚未在神经母细胞瘤中研究过此类多态性。考虑到这一点,我们进行了一项两中心病例对照研究,以评估中国儿童前体微小RNA中的基因变异与神经母细胞瘤易感性之间的关联,包括393例病例和812例对照。我们发现,miR-34b/c rs4938723 T>C多态性与神经母细胞瘤风险降低显著相关(TC与TT相比:调整后的比值比[OR]=0.51,95%置信区间[CI]=0.39-0.67;TC/CC与TT相比:调整后的OR=0.62,95%CI=0.48-0.79)。我们还观察到miR-218 rs11134527 A>G多态性与神经母细胞瘤风险降低之间存在显著关联(AG与AA相比:调整后的OR=0.73,95%CI=0.56-0.96)。分层分析进一步表明,rs4938723 T>C多态性的保护作用在各亚组中均很显著,无论年龄、性别和临床分期如何。就起源部位而言,这种多态性显著降低了起源于肾上腺的肿瘤风险。我们使用假阳性报告概率分析进一步验证了这些显著结果。总体而言,miR-34b/c rs4938723 T>C和miR-218 rs11134527 A>G多态性对神经母细胞瘤具有保护作用。这些发现需要进一步验证。