YTHDF1 gene polymorphisms and neuroblastoma susceptibility in Chinese children: an eight-center case-control study

Abstract

Neuroblastoma is one of the most common life-threatening extracranial tumors that mainly occurs in children, and its genetic etiology remains largely obscure. RNA m6A modification has been thought to play a key role in cancer progression. YTHDF1 is the critical downstream gene by which RNA m6A modification exerts its functions. Single nucleotide polymorphisms in the YTHDF1 gene may affect its expression and biological activity, thereby leading to abnormalities in the regulation of downstream m6A-modified RNA and eventually promoting the initiation and development of tumors. Here, we attempted to evaluate the contributions of two polymorphisms (rs6011668 C>T and rs6090311 A>G) in the YTHDF1 gene to neuroblastoma susceptibility in 898 cases and 1734 controls that originated in China. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the logistic regression models to evaluate the associations between selected polymorphisms and neuroblastoma risk. Overall, either in a single locus or combination analysis, no significant association with neuroblastoma risk was found for either of the two selected polymorphisms. However, the stratified analysis showed that rs6090311AG/GG genotypes significantly reduced the neuroblastoma risk in males (adjusted OR=0.77, 95% CI=0.62-0.96, P=0.018). Moreover, we found that subjects with 2 protective genotypes had a lower tumor risk in males than in those with 0-1 protective genotypes (adjusted OR=0.77, 95% CI=0.62-0.96, P=0.018). In summary, our study indicates that YTHDF1 gene polymorphisms may weakly contribute to neuroblastoma susceptibility. Our findings should be further verified by well-designed studies with larger sample sizes.

Comprehensive Analysis of Gene Signatures of m6ARNA Methylation Regulators in Lung Adenocarcinoma and Development of a Risk Scoring System

“…The modification of M6A methylation can regulate the functions of key downstream genes. Single nucleotide polymorphisms might affect gene expression and biological activity, leading to abnormal downstream m6A-RNA regulation, and subsequently promote tumor initiation and development [23]. In LUAD, M6A regulatory factors participate in the activation of signaling pathways in high-risk patients, such as cell circulation, DNA replication, RNA degradation, RNA polymerase, nucleotide excision repair, and basal transcription factors We previously evaluated the expression of 16 M6A regulatory-related genes in women with LUAD and the relationship between changes on these genes and clinical characteristics.…”

Characterization of m6A-related lncRNA signature in neuroblastoma

“…Furthermore, it has been shown that epigenetic alterations are closely associated with the development of NBL ( 30 – 33 ). Compounds targeting epigenetically modified proteins are increasingly evaluated as anticancer therapeutic agents, for m6A modifications involved in the development of NBL ( 34 , 35 ). One study suggested that risk models constructed from m6A-related mRNAs may effectively predict the prognosis of children with NBL ( 34 ).…”

YTHDF2 Gene rs3738067 A>G Polymorphism Decreases Neuroblastoma Risk in Chinese Children: Evidence From an Eight-Center Case-Control Study

“…This work was conducted with the approval of the Institutional Review Board of Guangzhou Women and Children's Medical Center, with 898 neuroblastoma patients registered in eight hospitals (Guangzhou, Zhengzhou, Wenzhou, Xi'an, Taiyuan, Kunming, Changsha, Shenyang) in China and 1,734 age- and gender-matched healthy controls involved in previous studies ( Supplementary Table S1 ) ( 20 , 21 ). All participants have signed informed consent.…”