Abstract
The genetic etiology of sporadic neuroblastoma remains largely obscure. RAN and RANBP2 genes encode Ras-related nuclear protein and Ran-binding protein 2, respectively. These two proteins form Ran-RanBP2 complex that regulate various cellular activities including nuclear transport. Aberrant functions of the two proteins are implicated in carcinogenesis. Given the unknown role of RAN/RANBP2 single nucleotide polymorphisms (SNPs) in neuroblastoma risk, we performed a multi-center case-control study in Chinese children to assess the association of the RAN/RANBP2 SNPs with neuroblastoma risk. We analyzed three potentially functional SNPs in RAN gene (rs56109543 C>T, rs7132224 A>G, rs14035 C>T) and one in RANBP2 (rs2462788 C>T) in 429 cases and 884 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to access the association between these four polymorphisms and neuroblastoma risk. No single variant was found to statistically significantly associate with neuroblastoma risk. However, individuals with 3 protective genotypes were less likely to develop neuroblastoma, in comparison to non-carriers (adjusted OR=0.33; 95% CI=0.12-0.96; P=0.042), as well as those with 0-2 protective genotypes (adjusted OR=0.33; 95% CI=0.11-0.94; P=0.038). Stratified analysis revealed no significant association for any of the four polymorphisms. Further studies are warranted to validate the weak impact of RAN/RANBP2 SNPs on neuroblastoma risk.
Highlights
Neuroblastoma is a common extracranial solid tumor that derives from neural crest progenitor cells [1, 2]
We performed the first investigation into the impact of single nucleotide polymorphisms (SNPs) in RAN/RANBP2 genes on the risk of neuroblastoma in Chinese Han children
Our data revealed that the single RAN or RANBP2 gene polymorphism might not be strong enough to confer the neuroblastoma susceptibility in Chinese children
Summary
Neuroblastoma is a common extracranial solid tumor that derives from neural crest progenitor cells [1, 2]. Neuroblastoma mostly takes place in children younger than 1 year, and the average diagnosis time is about 17 months of age [3]. 50% of neuroblastomas behave in highly malignant fashion, with distant metastasis at the time of diagnosis [8, 9]. Their 5-year survival rates remain less than 40% despite intensive, multi-modal therapy [10]. Several genome-wide association studies (GWASs) and the subsequent replication studies identified a number of neuroblastoma susceptibility alleles, including BARD1, LIN28B, HACE1, LMO1, MMP20 and CASC15 genes [16,17,18,19,20,21,22,23]. Candidate gene approaches detected the genetic associations of NEFL [24] and CDKN1B [25] gene polymorphisms with neuroblastoma susceptibility
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