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m7G修饰基因的遗传变异影响神经母细胞瘤易感性。

Genetic variants of m7G modification genes influence neuroblastoma susceptibility.

作者信息

Liu Jiabin, Deng Changmi, Lin Huiran, Zhang Xinxin, Zhu Jinhong, Zhou Chunlei, Wu Haiyan, He Jing

机构信息

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, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou 510623, Guangdong, China.

Faculty of Medicine, Macau University of Science and Technology, Macau 999078, China.

出版信息

Heliyon. 2023 Dec 12;10(1):e23658. doi: 10.1016/j.heliyon.2023.e23658. eCollection 2024 Jan 15.

Abstract

OBJECTIVE

Neuroblastoma is a life-threatening pediatric solid tumor whose etiology remains unclear. N7-methylguanosine (m7G) is one of the most important epigenetic modifications of RNA, which plays a crucial role in tumorigenesis. The m7G-mediated genes and also have been reported to be dysregulated in various cancers. However, the implications of and in neuroblastoma have not been clarified.

METHODS

Given the oncogenic potential of m7G modification, we performed a case-control study to assess the association of and genes polymorphisms with neuroblastoma risk in a Chinese population consisting of 402 cases and 473 controls. Odds ratios (ORs) and 95 % confidence intervals (CIs) were applied to evaluate the associations between studied polymorphisms and neuroblastoma risk. The adjusted odds ratio (AOR) was adjusted for age and gender.

RESULTS

Overall, four polymorphisms were significantly associated with neuroblastoma risk, including rs2291617 (recessive model: adjusted OR = 1.59, 95 % CI = 1.08-2.34,  = 0.019), rs2156316 (dominant model: adjusted OR = 0.74, 95 % CI = 0.57-0.97,  = 0.028), rs6586250 (dominant model: adjusted OR = 0.59, 95 % CI = 0.42-0.84,  = 0.004) and rs15736 (dominant model: adjusted OR = 0.60, 95 % CI = 0.42-0.85,  = 0.004). Stratified analysis showed stronger correlations between significant polymorphisms and neuroblastoma risk among subgroups divided by age, gender, tumor origin, and clinical stage. Furthermore, expression quantitative trait loci (eQTL) analysis revealed that significant polymorphisms were associated with the expression of the adjacent genes.

CONCLUSIONS

Our study indicated that four polymorphisms in m7G-mediated genes contribute to neuroblastoma susceptibility in the eastern Chinese population. However, our findings should be verified further by large-scale and well-designed studies.

摘要

目的

神经母细胞瘤是一种危及生命的儿科实体瘤,其病因尚不清楚。N7-甲基鸟苷(m7G)是RNA最重要的表观遗传修饰之一,在肿瘤发生中起关键作用。据报道,m7G介导的基因在各种癌症中也存在失调。然而,其在神经母细胞瘤中的意义尚未阐明。

方法

鉴于m7G修饰的致癌潜力,我们进行了一项病例对照研究,以评估402例病例和473例对照组成的中国人群中m7G介导的基因多态性与神经母细胞瘤风险的关联。应用比值比(OR)和95%置信区间(CI)来评估所研究的多态性与神经母细胞瘤风险之间的关联。调整后的比值比(AOR)针对年龄和性别进行了调整。

结果

总体而言,四个多态性与神经母细胞瘤风险显著相关,包括m7G相关基因1 rs2291617(隐性模型:调整后的OR = 1.59,95% CI = 1.08 - 2.34,P = 0.019)、m7G相关基因2 rs2156316(显性模型:调整后的OR = 0.74,95% CI = 0.57 - 0.97,P = 0.028)、m7G相关基因3 rs6586250(显性模型:调整后的OR = 0.59,95% CI = 0.42 - 0.84,P = 0.004)和m7G相关基因4 rs15736(显性模型:调整后的OR = 0.60,95% CI = 0.42 - 0.85,P = 0.004)。分层分析显示,在按年龄、性别、肿瘤起源和临床分期划分的亚组中,显著的多态性与神经母细胞瘤风险之间的相关性更强。此外,表达定量性状位点(eQTL)分析表明,显著的多态性与相邻基因的表达相关。

结论

我们的研究表明,m7G介导的基因中的四个多态性在中国东部人群中导致神经母细胞瘤易感性。然而,我们的发现应通过大规模且设计良好的研究进一步验证。

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