Ruizhong Zhang

XPG gene plays a critical role in the nucleotide excision repair pathway. However, the association between XPG gene polymorphisms and neuroblastoma risk has not been investigated. In this study with 256 neuroblastoma cases and 531 cancer-free controls, we investigated the effects of five potentially functional polymorphisms (rs2094258 C>T, rs751402 C>T, rs2296147 T>C, rs1047768 T>C and rs873601G>A) on neuroblastoma risk. We calculated odds ratio (OR) and 95% confidence interval (CI) to evaluate the association between the five selected polymorphisms and neuroblastoma risk. False-positive report probability (FPRP) was utilized to determine whether significant findings were noteworthy or because of a chance. We also performed genotype-phenotype association analysis to explore the biological plausibility of our findings. We found that the rs2094258 T allele was significantly associated with decreased neuroblastoma risk (CT versus CC: adjusted OR = 0.65, 95% CI = 0.47-0.90, P = 0.010; and CT/TT versus CC: adjusted OR = 0.71, 95% CI = 0.53-0.97, P = 0.030) after adjusting for age and gender. The association was more prominent for subjects with retroperitoneal tumour or early-stage tumour. We also found that carriers of the 2-3 risk genotypes had a significantly increased neuroblastoma risk when compared to carriers of the 0-1 risk genotypes. The association with risk genotypes was more predominant in older children, females and subjects with retroperitoneal tumour or early stage. Our results were further supported by FPRP analysis and genotype-phenotype association analysis. In conclusion, our study verified that the XPG gene rs2094258 C>T polymorphism may contribute to neuroblastoma susceptibility. Our findings require further validation by studies with larger sample size and concerning different ethnicities.

Neuroblastoma is a commonly occurring extracranial pediatric solid tumor without defined etiology. Polymorphisms in pre-miRNAs have been demonstrated to associate with the risk of several cancers. So far, no such polymorphism has been investigated in neuroblastoma. With this in mind, we performed a two-center case-control study to assess the association of genetic variants in pre-miRNAs and neuroblastoma susceptibility in Chinese children, including 393 cases and 812 controls. We found that miR-34b/c rs4938723 T > C polymorphism was significantly associated with decreased neuroblastoma risk (TC versus TT: adjusted odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.39-0.67; TC/CC versus TT: adjusted OR = 0.62, 95% CI = 0.48-0.79). We also observed the significant association between the miR-218 rs11134527 A > G polymorphism and decreased neuroblastoma risk (AG versus AA: adjusted OR = 0.73, 95% CI = 0.56-0.96). Stratified analysis further demonstrated that the protective effect of the rs4938723 T > C polymorphism remained prominent in the subgroups, regardless of age, gender, and clinical stages. In term of sites of origin, this polymorphism significantly reduced the risk of tumors originating from the adrenal gland. We further validated the significant results using false-positive report probability analyses. Overall, the miR-34b/c rs4938723 T > C and miR-218 rs11134527 A > G polymorphisms displayed a protective role from neuroblastoma. These findings need further validation.