RAN/RANBP2 polymorphisms and neuroblastoma risk in Chinese children: a three-center case-control study

Abstract

The genetic etiology of sporadic neuroblastoma remains largely obscure. <i>RAN</i> and <i>RANBP2</i> 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 <i>RAN/RANBP2</i> single nucleotide polymorphisms (SNPs) in neuroblastoma risk, we performed a multi-center case-control study in Chinese children to assess the association of the <i>RAN/RANBP2</i> SNPs with neuroblastoma risk. We analyzed three potentially functional SNPs in <i>RAN</i> gene (rs56109543 C>T, rs7132224 A>G, rs14035 C>T) and one in <i>RANBP2</i> (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; <i>P</i>=0.042), as well as those with 0-2 protective genotypes (adjusted OR=0.33; 95% CI=0.11-0.94; <i>P</i>=0.038). Stratified analysis revealed no significant association for any of the four polymorphisms. Further studies are warranted to validate the weak impact of <i>RAN/RANBP2</i> SNPs on neuroblastoma risk.