WTAP基因变异对肾母细胞瘤易感性的影响。

The contribution of WTAP gene variants to Wilms tumor susceptibility.

作者信息

Ma Li, Hua Rui-Xi, Lin Huiran, Zhu Jinhong, Fu Wen, Lin Ao, Zhang Jiao, Cheng Jiwen, Zhou Haixia, Li Suhong, Zhuo Zhenjian, 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, Guangzhou 510623, Guangdong, China; Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China.

出版信息

Gene. 2020 Sep 5;754:144839. doi: 10.1016/j.gene.2020.144839. Epub 2020 Jun 3.

DOI:10.1016/j.gene.2020.144839

PMID:32504654

Abstract

Wilms tumor is the most frequently occurring pediatric renal malignancy. Wilms tumor suppressor-1-associated protein (WTAP) is a vital component of N6-methyltransferase complex involved in tumorigenesis. However, the roles of WTAP gene single nucleotide polymorphisms (SNPs) in Wilms tumor risk have not been clarified to date. We successfully genotyped three WTAP gene SNPs using TaqMan assay in 405 Wilms tumor patients and 1197 cancer-free controls of Chinese children. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to determine the effects of WTAP gene SNPs on Wilms tumor risk. Carriers of the rs1853259 G variant are less susceptible to developing Wilms tumor, with an adjusted OR of 0.78 (AG vs. AA: 95% CI = 0.61-0.995, P = 0.046). Single locus analysis of rs9457712 G > A and rs7766006 G > T, as well as the combined analysis of risk genotypes, failed to unveil an association with Wilms tumor risk, respectively. Stratified analysis of the three SNPs and their combined risk effects showed more significant relationships with Wilms tumor risk under certain subgroups. In all, we found weak evidence of the association between WTAP gene SNPs and the risk of Wilms tumor. Further replication studies with greater sample size and different ethnicities are necessary to verify our findings.

摘要

肾母细胞瘤是最常见的儿童肾脏恶性肿瘤。肾母细胞瘤抑制因子1相关蛋白（WTAP）是参与肿瘤发生的N6 - 甲基转移酶复合物的重要组成部分。然而，WTAP基因单核苷酸多态性（SNP）在肾母细胞瘤风险中的作用迄今尚未阐明。我们使用TaqMan分析方法成功地对405例中国儿童肾母细胞瘤患者和1197例无癌对照儿童的三个WTAP基因SNP进行了基因分型。应用比值比（OR）和95%置信区间（CI）来确定WTAP基因SNP对肾母细胞瘤风险的影响。rs1853259 G变异携带者患肾母细胞瘤的易感性较低，校正后的OR为0.78（AG与AA相比：95% CI = 0.61 - 0.995，P = 0.046）。rs9457712 G>A和rs7766006 G>T的单基因座分析以及风险基因型的联合分析均未发现与肾母细胞瘤风险相关。对这三个SNP及其联合风险效应的分层分析显示，在某些亚组中与肾母细胞瘤风险的关系更为显著。总体而言，我们发现WTAP基因SNP与肾母细胞瘤风险之间存在关联的证据较弱。需要进行更大样本量和不同种族的进一步重复研究来验证我们的发现。