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

Jiabin Liu | Jiwen Cheng | Li Li | Yong Li | Haixia Zhou | Jiao Zhang | Suhong Li | Huimin Xia | Jing He | Zhonghua Yang
Journal of Cancer | 2021

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.

Pubmed ID: 33758623

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dbSNP (tool)

RRID:SCR_002338

Database as central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms. Distinguishes report of how to assay SNP from use of that SNP with individuals and populations. This separation simplifies some issues of data representation. However, these initial reports describing how to assay SNP will often be accompanied by SNP experiments measuring allele occurrence in individuals and populations. Community can contribute to this resource.

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NCBI (tool)

RRID:SCR_006472

A portal to biomedical and genomic information. NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease.

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SNPinfo Web Server (tool)

RRID:SCR_010589

SNPinfo Web Server is a set of freely available web-based SNP selection tools where investigators can specify genes or linkage regions and select SNPs based on GWAS results, linkage disequilibrium (LD), and predicted functional characteristics of both coding and non-coding SNPs. The algorithm uses GWAS SNP P-value data and finds all SNPs in high LD with GWAS SNPs, so that selection is from a much larger set of SNPs than the GWAS itself. The program can also identify and choose tag SNPs for SNPs not in high LD with any GWAS SNP. We incorporate functional predictions of protein structure, gene regulation, splicing and miRNA binding, and consider whether the alternative alleles of a SNP are likely to have differential effects on function. Users can assign weights for different functional categories of SNPs to further tailor SNP selection. The program accounts for LD structure of different populations so that a GWAS study from one ethnic group can be used to choose SNPs for one or more other ethnic groups. SNP Selection and Functional Information *Candidate Gene SNP Selection (GenePipe):SNP selection for candidate genes based on Genome Wide Association Study (GWAS) results, functional SNP prediction and Linkage Disequilibrium (LD) information. *GWAS Functional SNP Selection (GenomePipe):Functional SNP selection from SNPs that are in high LD with GWAS SNPs *GWAS SNP Selection in Linkage Loci (LinkagePipe):GWAS SNP selection in candidate genomic regions (such as linkage loci) *LD TAG SNP Selection (TagSNP):LD tag SNP selection and visualization for single or multiple populations. Finalization of SNP list from various queries. *SNP Function Prediction (FuncPred): Querying SNP function predictions and ethnic-specific allele frequencies. *SNP Information in DNA Sequence (SNPseq):Visualization of SNP related information in the context of DNA sequence. Preparing DNA Sequence for PCR Primer Design considering SNP information. Detailed information of CpG region.

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