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Purpose Neuroblastoma (NB) is the most common extracranial solid tumor found in children. To identify significant genetic factors for the risk of NB, several genetic studies was conducted mainly for Caucasians and Europeans. However, considering racial differences, there is a possibility that genetic predispositions that contribute to the development of NB are different, and genome-wide association study has not yet been conducted on Korean NB patients. Materials and Methods To identify the genetic variations associated with the risk of pediatric NB in Korean children, we performed a genome-wide association analysis with 296 NB patients and 1,000 unaffected controls (total n=1,296) after data cleaning and filtering as well as imputation of non-genotyped single nucleotide polymorphisms (SNPs) using IMPUTE v2.3.2. Results After adjusting for multiple comparisons, we found 21 statistically significant SNPs associated with the risk of NB (pcorr < 0.05) within 12 genes (RPTN, MRPS18B, LRRC45, KANSL1L, ARHGEF40, IL15RA, L1TD1, ANO7, LAMA5, OR7G2, SALL4, and NEUROG2). Interestingly, out of these, 12 markers were nonsynonymous SNPs. The SNP rs76015112 was most significantly associated with the risk of NB (p=8.1E-23, pcorr=2.3E-17) and was located in the RPTN gene. In addition, significant nonsynonymous SNPs in ADGRE1 were found in patients with MYCN amplification (rs7256147, p=2.6E-05). In high-risk group, rs7256147 was observed as a significant SNP (p=5.9E-06). Conclusion Our findings might facilitate improved understanding of the mechanism of pediatric NB pathogenesis. However, functional evaluation and replication of these results in other populations are still needed.
