Neuroblastoma susceptibility and association of N7-methylguanosine modification gene polymorphisms: multi-center case-control study.

Pediatr Res

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.

Published: June 2024

AI Article Synopsis

  • Neuroblastoma (NB) is a common childhood cancer, and variations in the METTL1/WDR4 genes may indicate risk for developing this disease.
  • Researchers analyzed genetic data from 898 NB patients and 1734 healthy controls to explore the link between METTL1/WDR4 gene polymorphisms and NB susceptibility.
  • While individual SNPs didn’t show strong associations, having a combination of protective WDR4 genotypes was linked to a reduced risk of NB, suggesting that these genetic variations could serve as biomarkers for identifying at-risk populations.

Article Abstract

Background: Neuroblastoma (NB) is a common extracranial solid malignancy in children. The N7-methylguanosine (mG) modification gene METTL1/WDR4 polymorphisms may serve as promising molecular markers for identifying populations susceptible to NB.

Methods: TaqMan probes was usded to genotype METTL1/WDR4 single nucleotide polymorphisms (SNPs) in 898 NB patients and 1734 healthy controls. A logistic regression model was utilized to calculate the odds ratio (OR) and 95% confidence interval (CI), evaluating the association between genotype polymorphisms and NB susceptibility. The analysis was also stratified by age, sex, tumor origin site, and clinical stage.

Results: Individual polymorphism of the METTL1/WDR4 gene investigated in this study did not show significant associations with NB susceptibility. However, combined genotype analysis revealed that carrying all 5 WDR4 protective genotypes was associated with a significantly lower NB risk compared to having 0-4 protective genotypes (AOR = 0.82, 95% CI = 0.69-0.96, P = 0.014). Further stratified analyses revealed that carrying 1-3 METTL1 risk genotypes, the WDR4 rs2156316 CG/GG genotype, the WDR4 rs2248490 CG/GG genotype, and having all five WDR4 protective genotypes were all significantly correlated with NB susceptibility in distinct subpopulations.

Conclusions: In conclusion, our findings suggest significant associations between mG modification gene METTL1/WDR4 SNPs and NB susceptibility in specific populations.

Impact: Genetic variation in mG modification gene is associated with susceptibility to NB. Single nucleotide polymorphisms in METTL1/WDR4 are associated with susceptibility to NB. Single nucleotide polymorphisms of METTL1/WDR4 can be used as a biomarker for screening NB susceptible populations.

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Source
http://dx.doi.org/10.1038/s41390-024-03318-wDOI Listing

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