Year: 2025
Type: article
Study design: Observational Study
Abstract: Neuroblastoma tightly linked with genetic abnormality. The core genes responsible for RNA N1-methyladenosine (m1A) modification are critical in tumor development. Nevertheless, few reports revealed the function of m1A modification core gene polymorphisms and the neuroblastoma risk. We carried out this study to verify the association of 12 single-nucleotide polymorphisms (SNPs) with neuroblastoma susceptibility. This study recruited 898 cases with newly diagnosed neuroblastoma and 1734 Healthy controls from eight medical centers. We selected 12 SNPs from m1A modification genes ALKBH1, TRMT6, TRMT61B, and TRMT10C, and genotypes were determined by the TaqMan method. We used univariable and multivariable logistic regression models to analyze the association of SNPs with neuroblastoma risk, followed by stratified analysis. Statistical analysis showed that TRMT6 rs236170 GG (AOR = 1.23, 95% CI = 1.02–1.50, P = 0.034), rs451571 CC (AOR = 1.46, 95% CI = 1.01–2.11, P = 0.043), rs236188 AA (AOR = 2.65, 95% CI = 1.16–6.07, P = 0.021), rs236110 AA (AOR = 1.91, 95% CI = 1.29–2.82, P = 0.001), and ALKBH1 rs6494 AA (AOR = 4.27, 95% CI = 1.31–13.93, P = 0.016), rs176942 GG (AOR = 1.98, 95% CI = 1.35–2.89, P = 0.0005) were neuroblastoma risk variants; the ALKBH1 rs1048147 CC (AOR = 0.80, 95% CI = 0.68–0.94, P = 0.007) was inverse associated with neuroblastoma risk. The eQTL analysis showed that functional annotation of rs6494 T > A may be potential function variants through decreasing ALKBH1 gene expression mRNA, rs451571 T > C, rs236188 G > A, rs236110 C > A are associated with neuroblastoma risk through increasing the expression of its nearby genes RP5-967N21.11 and lowering the expression of MCM8. Our research showed some SNPs in the m1A modification core genes are related to neuroblastoma. Clinical perspectives (i) Few reports have revealed the function of m1A modification core gene polymorphisms in neuroblastoma risk. (ii) After genotyping 12 SNPs with potential functions in four m1A modification core genes in children with neuroblastoma and healthy controls, we found several neuroblastoma predisposition loci, including TRMT6 rs236170, rs451571, rs236188, rs236110, and ALKBH1 rs6494, rs176942, and rs1048147. The eQTL assessment demonstrated that rs6494 T > A may be a potential functional variant by decreasing ALKBH1 mRNA expression. (iii) Our research is the first to reveal m1A modification core gene SNPs and neuroblastoma risk.
Source: BMC Cancer
Institutions: Peking University, Guangzhou Women and Children Medical Center, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Medical University, Hunan Children's Hospital, Harbin Medical University, Third Affiliated Hospital of Harbin Medical University, Sheng Jing Hospital, China Medical University, Zhengzhou University, First Affiliated Hospital of Zhengzhou University, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Kunming Children's Hospital, Wenzhou Medical University, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Shanxi Provincial Children's Hospital, Guangdong Pharmaceutical University
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,390
OpenAlex ID: W4415281643