Liu Jiabin, Cheng Jiwen, Li Li, Li Yong, Zhou Haixia, Zhang Jiao, Li Suhong, Xia Huimin, He Jing, Yang Zhonghua
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Department of Pediatric Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China.
J Cancer. 2021 Mar 5;12(8):2465-2471. doi: 10.7150/jca.54496. eCollection 2021.
Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. is the critical downstream gene by which RNA m6A modification exerts its functions. Single nucleotide polymorphisms in the gene may affect its expression and biological activity, thereby leading to abnormalities in the regulation of downstream m6A-modified RNA and eventually promoting the initiation and development of tumors. Here, we attempted to evaluate the contributions of two polymorphisms (rs6011668 C>T and rs6090311 A>G) in the gene to neuroblastoma susceptibility in 898 cases and 1734 controls that originated in China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic regression models to evaluate the associations between selected polymorphisms and neuroblastoma risk. Overall, either in a single locus or combination analysis, no significant association with neuroblastoma risk was found for either of the two selected polymorphisms. However, the stratified analysis showed that rs6090311AG/GG genotypes significantly reduced the neuroblastoma risk in males (adjusted OR=0.77, 95% CI=0.62-0.96, =0.018). Moreover, we found that subjects with 2 protective genotypes had a lower tumor risk in males than in those with 0-1 protective genotypes (adjusted OR=0.77, 95% CI=0.62-0.96, =0.018). In summary, our study indicates that gene polymorphisms may weakly contribute to neuroblastoma susceptibility. Our findings should be further verified by well-designed studies with larger sample sizes.
神经母细胞瘤是最常见的危及生命的颅外肿瘤之一,主要发生于儿童,其遗传病因在很大程度上仍不清楚。RNA m6A修饰被认为在癌症进展中起关键作用。 是RNA m6A修饰发挥其功能的关键下游基因。该基因中的单核苷酸多态性可能影响其表达和生物学活性,从而导致下游m6A修饰的RNA调控异常,最终促进肿瘤的发生和发展。在此,我们试图评估该基因中的两个多态性(rs6011668 C>T和rs6090311 A>G)对来自中国的898例病例和1734例对照中神经母细胞瘤易感性的影响。在逻辑回归模型中计算优势比(OR)和95%置信区间(CI),以评估所选多态性与神经母细胞瘤风险之间的关联。总体而言,无论是单基因座分析还是联合分析,所选的两个多态性均未发现与神经母细胞瘤风险有显著关联。然而,分层分析显示,rs6090311 AG/GG基因型显著降低了男性患神经母细胞瘤的风险(调整后的OR=0.77,95%CI=0.62-0.96, =0.018)。此外,我们发现具有2种保护基因型的男性受试者比具有0-1种保护基因型的男性受试者患肿瘤的风险更低(调整后的OR=0.77,95%CI=0.62-0.96, =0.018)。总之,我们的研究表明, 基因多态性可能对神经母细胞瘤易感性有微弱影响。我们的发现应通过样本量更大的精心设计的研究进一步验证。