NSUN2 gene rs13181449 C>T polymorphism reduces neuroblastoma risk

Neuroblastoma is the most common tumor in infants. RNA m5C modification regulates the survival, differen-tiation, and migration of cells affecting RNA function. However, the effects of the m5C modification methyl-transferase gene NSUN2 polymorphism on neuroblastoma susceptibility have not been reported. TaqMan method was used to determine genotypes of four NSUN2 polymorphisms (rs4702373 C>T, rs13181449 C>T, rs166049 T>G, and rs8192120 A>C) in 402 patients with neuroblastoma and 473 cancer-free controls from Jiangsu province, China. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association of NSUN2 polymorphisms with neuroblastoma susceptibility. The association was also further assessed in sub-groups stratified by age, sex, tumor origin, and stage. GTEx was used to analyze the effect of these poly-morphisms on NSUN2 expression. We found the rs13181449 C>T was significantly associated with reduced neuroblastoma risk (CT vs. CC: adjusted OR = 0.68, 95% CI = 0.51-0.92, P = 0.012; CT/TT vs. CC: adjusted OR = 0.70, 95% CI = 0.53-0.92, P = 0.010). Compared with 0-2 protective genotypes, those with 3-4 protective genotypes could significantly reduce the neuroblastoma risk (adjusted OR = 0.68, 95% CI = 0.52 to 0.90, P = 0.006). Stratification analysis showed that the protective effect of rs13181449 polymorphism remained signif-icant in children with age >18 months, boys, and those with early INSS stages. Moreover, children with more protective genotypes in the same subgroups also exhibited significantly reduced neuroblastoma risk. GTEx analysis showed that the rs13181449 T genotype was related with decreased NSUN2 gene expression. In con-clusions, NSUN2 rs13181449 polymorphism is associated with decreased neuroblastoma risk, and the underlying mechanism in neuroblastoma needs further study.

Automated summary

In this study, the association between NSUN2 rs13181449 polymorphism and neuroblastoma susceptibility was investigated in a Chinese population. The results showed that the rs13181449 polymorphism was significantly associated with a reduced risk of neuroblastoma. Further analysis revealed that this protective effect was observed in children with age >18 months, boys, and those with early INSS stages.