METTL14 Gene Polymorphisms Confer Neuroblastoma Susceptibility: An Eight-Center Case-Control Study

Neuroblastoma is the primary cause of cancer death in childhood. METTL14 is tightly linked to cancer. However, whether single-nucleotide polymorphisms (SNPs) in the METTL14 gene could predispose to neuroblastoma susceptibility lacks evidence. With an epidemiology case-control study, associations between METTL14 gene SNPs and overall risk for neuroblastoma were estimated in 898 cases and 1,734 controls. Following that, stratified analysis was performed. Among the five analyzed SNPs, rs298982 G>A and rs62328061 A>G exhibited a significant association with decreased susceptibility to neuroblastoma, whereas the associations with increased neuroblastoma susceptibility were observed for rs9884978 G>A and rs4834698 T>C. Moreover, subjects carrying two to five risk genotypes were more inclined to develop neuroblastoma than those with zero to one risk genotypes. The stratified analysis further demonstrated the protective effect of rs298982 G>A and rs62328061 A>G, as well as the predisposing effect of rs4834698 T>C and two to five risk genotypes, in certain subgroups. Haplotype analysis was performed. Moreover, false-positive report probability analysis validated the reliability of the significant results. The expression quantitative trait locus analysis revealed that rs298982 is correlated with the expression levels of its surrounding genes. Our results suggest that some SNPs in the METTL14 gene are associated with predisposition to neuroblastoma. [Display omitted] The role of m6A modification METTL14 gene SNPs in neuroblastoma remains to be elucidated. He and colleagues found that METTL14 gene SNPs are associated with predisposition to neuroblastoma, possibly by influencing the expression levels of its surrounding genes. Their work shed some light on the genetic etiology of neuroblastoma.