Association between METTL3 gene polymorphisms and neuroblastoma susceptibility: A nine-centre case-control study

Neuroblastoma ranks as the most commonly seen and deadly solid tumour in infancy. The aberrant activity of m⁶ A-RNA methyltransferase METTL3 is involved in human cancers. Therefore, functional genetic variants in the METTL3 gene may contribute to neuroblastoma risk. In the current nine-centre case-control study, we aimed to analyse the association between the METTL3 gene single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We genotyped four METTL3 gene SNPs (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G, and rs1263801 G>C) in 968 neuroblastoma patients and 1814 controls in China. We found significant associations between these SNPs and neuroblastoma risk in neither single-locus nor combined analyses. Interestingly, in the stratified analysis, we observed a significant risk association with rs1061027 AA in subgroups of children ≤ 18 months of age (adjusted OR = 1.87, 95% CI = 1.03-3.41, P = .040) and females (adjusted OR = 1.86, 95% CI = 1.07-3.24, P = .028). Overall, we identified a significant association between METTL3 gene rs1061027 C>A polymorphism and neuroblastoma risk in children ≤18 months of age and females. Our findings provide novel insights into the genetic determinants of neuroblastoma.