Functional polymorphisms in HOGG1 gene and neuroblastoma risk in Chinese children

Abstract

Neuroblastoma is a lethal tumor of the sympathetic nervous system. 8-Hydroxydeoxyguanine (8-OH-dG) formation is a common seen type of oxidative DNA damage, which could be repaired by human oxoguanine glycosylase 1 (hOGG1). To explore the contributing role of hOGG1 gene single nucleotide polymorphisms (SNPs) in neuroblastoma risk, we performed a case-control study by genotyping three SNPs (rs1052133 G>C, rs159153 T>C, rs293795 A>G) in hOGG1 gene. A total of 512 neuroblastoma cases and 1076 cancer-free controls were enrolled from three medical centers in China. The hOGG1 gene polymorphisms were determined using TaqMan real-time PCR. The results showed that only the rs1052133 G>C polymorphism was associated with neuroblastoma risk [GC vs. GG: adjusted odds ratio (OR)=0.64, 95% confidence interval (CI)=0.51-0.81, P=0.0002; dominant model: adjusted OR=0.71, 95% CI=0.57-0.88, P=0.002]. Moreover, subjects carrying 1, 2, or 1-3 protective genotypes have less opportunity to develop neuroblastoma, in comparison to those without protective genotypes. Stratified analysis revealed that rs1052133 GC/CC carriers were less likely to develop neuroblastoma in subgroups of age >18 months, males, tumor that develops from retroperitoneal, mediastinum and clinical stage I+II+4s. Our results indicate that hOGG1 rs1052133 G>C polymorphism is associated with decreased risk of neuroblastoma. However, the exact biological mechanism awaits further research.