Neuroblastoma (NB) is the most common extracranial tumor in children. YTHDC1, a member of RNA methylation modification binding proteins, plays critical roles in tumor occurrence and metastasis. However, it is unclear whether YTHDC1 gene polymorphisms are related to NB susceptibility. Herein, we aimed to evaluate the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C, rs3813832 T>C) and susceptibility of NB by logistic regression models. In this eight-center case-control study, 898 patients with NB and 1734 healthy controls were genotyped by TaqMan assay. The results showed that rs3813832 TC genotype could significantly reduce the susceptibility of NB compared with the TT genotype [adjusted odds ratio (AOR) = 0.81, 95% confidence interval (CI) = 0.68-0.96, P = 0.018]. Combined genotype analysis revealed that individuals with 3 protective genotypes had a prominently lower NB risk than those with 0-2 protective genotypes (AOR = 0.80, 95% CI = 0.68-0.94, P = 0.006). The stratified analysis also demonstrated the protective effect of rs3813832 TC/CC and 3 protective genotypes in certain subgroups. Further functional experiments revealed that YTHDC1 siRNA-554, targeting the area near the rs3813832 T>C polymorphism site, could observably inhibit the proliferation and migration of NB cells. In conclusion, our findings highlight the involvement of YTHDC1 gene and its genetic variants in the etiology of NB.
Keywords: YTHDC1; m6A; neuroblastoma; polymorphism; susceptibility.