LAUSR

Neuroblastoma is a childhood cancer that originates in the developing sympathetic nervous system. We previously reported a crucial role of mitochondrial DNA (mtDNA) haplogroups in the pathology of neuroblastoma. To pinpoint mtDNA variants associated with neuroblastoma risk, we applied a mitochondrial genome imputation pipeline to the SNP array data of two pediatric cohorts containing a total of 2,404 neuroblastoma cases and 9,310 cancer-free controls. All statistical tests were 2-sided. The single nucleotide variant, rs2853493, was statistically significantly associated with neuroblastoma risk in the discovery cohort (odds ratio = 0.62, 95% CI = 0.53-0.72, P < .001) and further confirmed in the replication cohort (odds ratio = 0.75, 95% CI = 0.62-0.90, P = .002). Further, eQTL analysis indicated genotypes of rs2853493 were associated with expression levels of MT-CYB gene expression in neuroblastoma cells suggesting rs2853493 may confer risk to neuroblastoma via regulating the expression level of its nearby genes.