5-methylcytosine RNA modification is a key regulator of neuroblastoma oncogenesis and differentiation. NSUN6, a 5-methylcytosine-specific messenger RNA methyltransferase, modulates messenger RNA methyltransferase activity and translation termination. Yet, its potential link to neuroblastoma risk has not been previously reported. The present study aimed to reveal the relationship between NSUN6 gene polymorphisms and the risk of neuroblastoma in children from Jiangsu province.
Methods
In this case-control study, we investigated three NSUN6 gene polymorphisms (rs3740102 A>C, rs12780826 T>A, and rs61842187 G>C) in 402 neuroblastoma cases and 473 controls, all of whom were children from Nanjing City, Jiangsu Province, China. DNA from these subjects was assessed using the TaqMan method. Multivariate logistic regression analysis was employed to examine the association between NSUN6 gene polymorphisms and neuroblastoma risk. Additionally, the Genotype-Tissue Expression database was utilized to elucidate the impact of these polymorphisms on NSUN6 and nearby gene expression. Kaplan-Meier analysis and the non-parametric test were conducted on the R2 platform to assess the relationship between gene expression, prognosis, and neuroblastoma risk.
Results
Carriage of two to three protective genotypes (rs3740102 AA/AC, rs12780826 TT/TA, rs61842187 CC) was significantly associated with a lower risk of neuroblastoma (adjusted odds ratio = 0.41, 95% confidence interval = 0.23–0.73, P = 0.002), with consistent results across all subgroups. Expression quantitative trait locus analysis showed these single-nucleotide polymorphisms may upregulate the expression of NSUN6 and CACNB2. Furthermore, higher NSUN6 and CACNB2 expression was correlated with a potentially lower risk of neuroblastoma, improved overall survival (NSUN6: P = 2.54e-03; CACNB2: P = 6.35e-06) and event-free survival (NSUN6: P = 7.90e-04; CACNB2: P = 4.64e-06), as well as a lower likelihood of MYCN amplification.
Conclusions
NSUN6 rs3740102 AA/AC, rs12780826 TT/TA, and rs61842187 CC genotypes may be associated with a better prognosis of neuroblastoma. This association may be related to the potential upregulation of NSUN6 gene expression and a lower likelihood of MYCN amplification.
Full text
https://www.xiahepublishing.com/2835-3315/CSP-2025-00019
The study was recently published in the Cancer Screening and Prevention .
Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.
