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中国儿童基因多态性与肾母细胞瘤易感性:一项五中心病例对照研究。

gene polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study.

作者信息

Deng Linqing, Hua Rui-Xi, Deng Changmi, Zhu Jinhong, Zhang Zhengtao, Cheng Jiwen, Zhang Jiao, Zhou Haixia, Li Suhong, Ruan Jichen, Liu Guochang, He Jing, Fu Wen

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.

Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.

出版信息

J Cancer. 2023 May 8;14(8):1293-1300. doi: 10.7150/jca.83747. eCollection 2023.

Abstract

Wilms tumor is the most common embryonal renal malignancy in children. WDR4 is an indispensable noncatalytic subunit of the RNA N7-methylguanosine (m7G) methyltransferase complex and plays an essential role in tumorigenesis. However, the relationship between polymorphisms in the gene and susceptibility to Wilms tumor remains to be fully investigated. We performed a large case-control study involving 414 patients and 1199 cancer-free controls to investigate whether single nucleotide polymorphisms (SNPs) in the gene are associated with Wilms tumor susceptibility. gene polymorphisms (rs2156315 C > T, rs2156316 C > G, rs6586250 C > T, rs15736 G > A, and rs2248490 C > G) were genotyped using the TaqMan assay. In addition, unconditioned logistic regression analysis was performed, odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between gene SNPs and Wilms tumor susceptibility as well as the strength of the associations. We found that only the rs6586250 C>T polymorphism was significantly associated with an increased risk of Wilms tumor (adjusted OR=2.99, 95% CI = 1.28-6.97, = 0.011 for the rs6586250 TT genotype; adjusted OR=3.08, 95% CI = 1.33-7.17, = 0.009 for the rs6586250 CC/CT genotype). Furthermore, the stratification analysis revealed that patients with the rs6586250 TT genotype and carriers with 1-5 risk genotypes exhibited statistically significant associations with increased Wilms tumor risk in specific subgroups. However, the rs2156315 CT/TT genotype was identified as having a protective effect against Wilms tumor in the age >18 months subgroup compared with the rs2156315 CC genotype. In brief, our study demonstrated that the rs6586250 C > T polymorphism of the gene was significantly associated with Wilms tumor. This finding may contribute to the understanding of the genetic mechanism of Wilms tumor.

摘要

肾母细胞瘤是儿童最常见的胚胎性肾恶性肿瘤。WDR4是RNA N7-甲基鸟苷(m7G)甲基转移酶复合物中不可或缺的非催化亚基,在肿瘤发生中起重要作用。然而,该基因多态性与肾母细胞瘤易感性之间的关系仍有待充分研究。我们进行了一项大型病例对照研究,纳入414例患者和1199例无癌对照,以调查该基因的单核苷酸多态性(SNP)是否与肾母细胞瘤易感性相关。使用TaqMan分析对该基因多态性(rs2156315 C>T、rs2156316 C>G、rs6586250 C>T、rs15736 G>A和rs2248490 C>G)进行基因分型。此外,进行了非条件逻辑回归分析,使用优势比(OR)和95%置信区间(CI)评估该基因SNP与肾母细胞瘤易感性之间的关联以及关联强度。我们发现,只有rs6586250 C>T多态性与肾母细胞瘤风险增加显著相关(rs6586250 TT基因型的调整后OR=2.99,95%CI=1.28-6.97,P=0.011;rs6586250 CC/CT基因型的调整后OR=3.08,95%CI=1.33-7.17,P=0.009)。此外,分层分析显示,rs6586250 TT基因型患者和携带1-5种风险基因型的携带者在特定亚组中与肾母细胞瘤风险增加存在统计学显著关联。然而,与rs2156315 CC基因型相比,rs2156315 CT/TT基因型在年龄>18个月的亚组中被确定对肾母细胞瘤具有保护作用。简而言之,我们的研究表明该基因的rs6586250 C>T多态性与肾母细胞瘤显著相关。这一发现可能有助于理解肾母细胞瘤的遗传机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5124/10240673/3e86991ffce4/jcav14p1293g001.jpg

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