miRNA-Processing Gene Variants and Neuroblastoma Susceptibility: A Pilot Case-Control Study

Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children, but the inherited factors influencing susceptibility are not fully understood. Given the link between defective microRNA biogenesis and aggressive NB, germline variants in key miRNA-processing genes are plausible candidate modifiers. This pilot case-control study aimed to assess whether five selected SNPs in DICER1, DROSHA, and AGO1 are associated with NB susceptibility in a Greek pediatric population. Materials and methods: This exploratory case-control study included 200 children from Crete, Greece, comprising 25 with NB and 175 healthy controls recruited during routine health visits. Five SNPs in DICER1, DROSHA, and AGO1 genes were genotyped using TaqMan assays. Logistic regression analyses were adjusted for age and sex, with multiple testing corrections applied via Bonferroni and false discovery rate (FDR) methods. Due to the limited number of NB cases, analyses within this group were considered exploratory. Results: In the adjusted primary analyses, DROSHA rs3805500 demonstrated the strongest association with NB susceptibility (per G allele OR 3.43, 95% CI 1.69-6.94) and remained significant after Bonferroni and FDR corrections. DROSHA rs642321 showed a nominal association that did not retain significance after correction for multiple testing, while DICER1 rs3742330 exhibited a borderline association in the adjusted model. No significant associations were observed for AGO1 rs636832 or DROSHA rs10035440. Exploratory within-case analyses provided limited descriptive insights and require validation in larger cohorts. Conclusions: This pilot study suggests that genetic variations in the miRNA-processing pathway may affect NB susceptibility. Further research involving larger, ethnically diverse cohorts, along with expanded genotype-expression analyses and functional validation, is essential before clinical or prognostic applications can be established.