Evaluation of Genetic Predisposition for MYCN-Amplified Neuroblastoma.

ABSTRACT: To investigate genetic predispositions for MYCN-amplified neuroblastoma, we performed a meta-analysis of three genome-wide association studies totaling 615 MYCN-amplified high-risk neuroblastoma cases and 1869 MYCN-nonamplified non-high-risk neuroblastoma cases as controls using a fixed-effects model with inverse variance weighting. All statistical tests were two-sided. We identified a novel locus at 3p21.31 indexed by the single nucleotide polymorphism (SNP) rs80059929 (odds ratio [OR] = 2.95, 95% confidence interval [CI] = 2.17 to 4.02, Pmeta = 6.47?×?10-12) associated with MYCN-amplified neuroblastoma, which was replicated in 127 MYCN-amplified cases and 254 non-high-risk controls (OR?=?2.30, 95% CI?=?1.12 to 4.69, Preplication = .02). To confirm this signal is exclusive to MYCN-amplified tumors, we performed a second meta-analysis comparing 728 MYCN-nonamplified high-risk patients to identical controls. rs80059929 was not statistically significant in MYCN-nonamplified high-risk patients (OR?=?1.24, 95% CI?=?0.90 to 1.71, Pmeta = .19). SNP rs80059929 is within intron 16 in the KIF15 gene. Additionally, the previously reported LMO1 neuroblastoma risk locus was statistically significant only in patients with MYCN-nonamplified high-risk tumors (OR?=?0.63, 95% CI?=?0.53 to 0.75, Pmeta = 1.51?×?10-8; Pmeta = .95). Our results indicate that common genetic variation predisposes to different neuroblastoma genotypes, including the likelihood of somatic MYCN-amplification.

SUBMITTER: Hungate EA 

PROVIDER: S-EPMC6279278 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature