Abstract
Neuroblastoma (NB) is the most common extracranial tumor in children. YTHDC1, a member of RNA methylation modification binding proteins, plays critical roles in tumor occurrence and metastasis. However, it is unclear whether YTHDC1 gene polymorphisms are related to NB susceptibility. Herein, we aimed to evaluate the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C, rs3813832 T>C) and susceptibility of NB by logistic regression models. In this eight-center case-control study, 898 patients with NB and 1734 healthy controls were genotyped by TaqMan assay. The results showed that rs3813832 TC genotype could significantly reduce the susceptibility of NB compared with the TT genotype [adjusted odds ratio (AOR) = 0.81, 95% confidence interval (CI) = 0.68–0.96, P = 0.018]. Combined genotype analysis revealed that individuals with 3 protective genotypes had a prominently lower NB risk than those with 0-2 protective genotypes (AOR = 0.80, 95% CI = 0.68–0.94, P = 0.006). The stratified analysis also demonstrated the protective effect of rs3813832 TC/CC and 3 protective genotypes in certain subgroups. Further functional experiments revealed that YTHDC1 siRNA-554, targeting the area near the rs3813832 T>C polymorphism site, could observably inhibit the proliferation and migration of NB cells. In conclusion, our findings highlight the involvement of YTHDC1 gene and its genetic variants in the etiology of NB.
Highlights
Neuroblastoma (NB) is the most common extracranial solid tumor in children, accounting for 8% of all pediatric malignancies [1]
The results showed that in the rs3813832 T>C polymorphism, relative to the TT genotype, TC genotype could significantly reduce the susceptibility of NB [adjusted odds ratio (AOR) = 0.81, 95% confidence interval (CI) = 0.68–0.96, P = 0.018]
The combined genotype analysis revealed that individuals carrying 3 protective genotypes had a prominent lower risk of NB compared with individuals carrying 0–2 protective genotypes (AOR = 0.80, 95% CI = 0.68–0.94, P = 0.006)
Summary
Neuroblastoma (NB) is the most common extracranial solid tumor in children, accounting for 8% of all pediatric malignancies [1]. High-risk patients, accounting for nearly 50% of NB, have been extensively metastatic at the time of diagnosis. Despite various treatments such as surgery, chemotherapy, radiotherapy, and immunotherapy, the survival rate is still less than 40% [4]. Many polymorphisms were identified to influence chemotherapy and outcome in patients with neuroblastoma [20, 21]. The identification of these susceptible loci has deepened the understanding of the pathogenesis of NB [22, 23]. More gene single nucleotide polymorphisms (SNPs) involved in the process of tumorigenesis await to be revealed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
