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, Guangdong, China.
Department of Clinical Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang, Hangzhou, China.
J Gene Med. 2020 Nov;22(11):e3255. doi: 10.1002/jgm.3255. Epub 2020 Aug 7.
Wilms tumor is a common pediatric tumor worldwide. Methyltransferase like 3 (METTL3) is a core gene of the N -methyladenosine (m A) modification that widely affects the transcription of tumor-related genes in eukaryotes. METTL3 has been extensively investigated in various tumors but not Wilms tumor.
We describe a five-center case-control study with 414 patients and 1199 controls aiming to explore the associations between METTL3 polymorphisms (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G and rs1263801 G>C) and Wilms tumor susceptibility. A TaqMan real-time polymerase chain reaction was performed for genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported as evaluation indicators to determine any associations.
Referring to the preliminary analysis results, protective genotypes were identified as rs1061026 TG/GG, rs1061027 CA/AA, rs1139130 GG and rs1263801 GC/CC. The children with three protective genotypes were less likely to develop Wilms tumor than children without protective genotypes (adjusted OR = 0.68, 95% CI = 0.46-0.999, p = 0.0496). Similarly, stratified analysis of the subgroup aged > 18 months, carrying 3 or 4 protective genotypes, was a protective factor for Wilms tumor compared to carrying 0-2 protective genotypes (adjusted OR = 0.59 95% CI = 0.39-0.91, p = 0.016). However, we did not observe any other significant results.
The combined effect of METTL3 polymorphisms reduce Wilms tumor susceptibility in Chinese children. This conclusion requires further verification.
Wilms 瘤是一种常见的小儿肿瘤，在全球范围内都有发生。甲基转移酶样 3（METTL3）是 N6-甲基腺苷（m A）修饰的核心基因，广泛影响真核生物中与肿瘤相关基因的转录。METTL3 已在各种肿瘤中得到广泛研究，但在 Wilms 瘤中尚未得到研究。
我们描述了一项由五个中心参与的病例对照研究，共有 414 例患者和 1199 例对照，旨在探讨 METTL3 多态性（rs1061026 T>G、rs1061027 C>A、rs1139130 A>G 和 rs1263801 G>C）与 Wilms 肿瘤易感性之间的关系。采用 TaqMan 实时聚合酶链反应进行基因分型。比值比（OR）和 95%置信区间（CI）被报告为评估指标，以确定任何关联。
根据初步分析结果，鉴定出保护性基因型为 rs1061026 TG/GG、rs1061027 CA/AA、rs1139130 GG 和 rs1263801 GC/CC。与没有保护性基因型的儿童相比，携带三种保护性基因型的儿童发生 Wilms 肿瘤的可能性较低（调整 OR=0.68，95%CI=0.46-0.999，p=0.0496）。同样，对年龄>18 个月的亚组进行分层分析，与携带 0-2 种保护性基因型相比，携带 3 或 4 种保护性基因型是 Wilms 肿瘤的保护因素（调整 OR=0.59，95%CI=0.39-0.91，p=0.016）。然而，我们没有观察到任何其他显著结果。
METTL3 多态性的联合作用降低了中国儿童患 Wilms 肿瘤的易感性。这一结论需要进一步验证。
