Background: Neuroblastoma, mainly affecting children, is a lethal malignancy arising from the developing sympathetic nervous system. The genetic etiology of neuroblastoma remains mostly obscure. High mobility group AT-hook 2 (HMGA2), an oncogenic gene, is up-regulated in many tumors. Single nucleotide polymorphisms (SNPs) often modify cancer susceptibility. However, no studies are investigating the association between HMGA2  SNPs and neuroblastoma susceptibility.
Methods: We conducted a four-center case-control study to evaluate the association between three HMGA2  polymorphisms (rs6581658 A>G, rs8756 A>C and rs968697 T>C) and neuroblastoma susceptibility in a Chinese population with 505 cases and 1070 controls. Logistic regression was performed to evaluate the strength of the association.
Results: We found that the rs8756 AC/CC genotypes were associated with a reduced neuroblastoma risk when compared to rs8756 AA genotype [Adjusted odds ratio (OR)=0.74, 95% confidence interval (CI)=0.56– 0.99, P =0.039]. Carriers with 3 protective genotypes have lower neuroblastoma susceptibility than those without or with 0– 2 protective genotypes. The stratified analysis revealed that the protective effects of rs8756 AC/CC genotypes were more predominant among children of age > 18 months, males, and subgroups with the tumor in the mediastinum. Furthermore, haplotype analysis uncovered that haplotype ACC significantly reduced neuroblastoma risk.
Conclusion: Our study indicated HMGA2  rs8756 A>C polymorphism is significantly associated with decreased neuroblastoma risk.
Keywords: neuroblastoma, susceptibility, HMGA2 , polymorphism