Date Published: April 28, 2018
Publisher: Impact Journals
Author(s): Juxiang Wang, Zhenjian Zhuo, Min Chen, Jinhong Zhu, Jie Zhao, Jiao Zhang, Shanshan Chen, Jing He, Haixia Zhou.
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.
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 . Neuroblastoma is characterized by a wide range of variable prognosis, spanning from spontaneous regression without chemotherapy to life-threatening tumor progression despite intensive treatment [4–7]. Approximately 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 .
In the current study, we performed the first investigation into the impact of 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. However, three protective RAN genotypes were observed to cumulatively reduce the risk of neuroblastoma.