METTL3 polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study

J Gene Med. 2020 Nov;22(11):e3255. doi: 10.1002/jgm.3255. Epub 2020 Aug 7.

Abstract

Background: Wilms tumor is a common pediatric tumor worldwide. Methyltransferase like 3 (METTL3) is a core gene of the N6 -methyladenosine (m6 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.

Methods: 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.

Results: 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.

Conclusions: The combined effect of METTL3 polymorphisms reduce Wilms tumor susceptibility in Chinese children. This conclusion requires further verification.

Keywords: METTL3; Wilms tumor; m6A; polymorphism; susceptibility.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Case-Control Studies
  • China
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Infant
  • Kidney Neoplasms / etiology
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Methyltransferases / genetics*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Wilms Tumor / etiology
  • Wilms Tumor / metabolism
  • Wilms Tumor / pathology*

Substances

  • Methyltransferases
  • METTL3 protein, human