Increased risk of neuroblastoma in Chinese children from Jiangsu province with NSUN4 gene rs10736428 A>C polymorphism.

Objective: Modification of 5-methylcytosine (m5C) exerts regulatory effects on RNA functionality, governing critical processes that include cell migration, survival, and differentiation. NSUN4, a demethylase responsible for generating the m5C modification, plays a pivotal role in carcinogenesis and cellular differentiation. To date, there have been no documented reports on the role of NSUN4 gene polymorphisms in neuroblastoma.

Methods: The authors investigated 402 neuroblastoma patients and 473 control subjects and identified 4 potential functional polymorphisms (rs10736428 A>C, rs3737744 G>A, rs10252 G>A, and rs41294484 C>T) with the TaqMan assay. Logistic regression analysis assessed the correlation in terms of the OR and 95% CI. Furthermore, rs10736428 and rs41294484 were stratified to assess their potential associations with increased risk of neuroblastoma.

Results: Individuals carrying the rs10736428 CC genotype exhibited a markedly increased risk of neuroblastoma development (adjusted OR 2.06, 95% CI 1.02-4.14, p = 0.044). Further stratified analyses revealed that individuals with the rs10736428 CC genotype exhibited heightened predisposition to neuroblastoma, particularly within the subgroups of male patients, patients with mediastinal tumors, and patients with tumors classified under the International Neuroblastoma Staging System as stages 3 and 4. Moreover, children with 1-4 risk genotypes also showed positive associations with mediastinal tumors.

Conclusions: A strong association between the NSUN4 rs10736428 polymorphism and increased susceptibility to neuroblastoma has been identified.