HMGA2 Polymorphisms and Hepatoblastoma Susceptibility: A Five-Center Case-Control Study

Background: Hepatoblastoma is a rare disease. Its etiology remains obscure. No epidemiological reports have assessed the relationship of High Mobility Group A2 (HMGA2) single nucleotide polymorphisms (SNPs) with hepatoblastoma risk. This case-control study leads as a pioneer to explore whether HMGA2 SNPs (rs6581658 A>G, rs8756 A>C, rs968697 T>C) could impact hepatoblastoma risk. Methods: We acquired samples from 275 hepatoblastoma cases and 1018 controls who visited one of five independent hospitals located in the different regions of China. The genotyping of HMGA2 SNPs was implemented using the PCR-based TaqMan method, and the risk estimates were quantified by odds ratios (ORs) and 95% confidence intervals (CIs). Results: In the main analysis, we identified that rs968697 T>C polymorphism was significantly related to hepatoblastoma risk in the additive model (adjusted OR=0.73, 95% CP0.54-0.98, P=0.035). Notably, participants carrying 2-3 favorable genotypes had reduced hepatoblastoma risk (adjusted OR=0.71, 95% CP0.52-0.96, P=0.028) in contrast to those carrying 0-1 favorable genotypes. Furthermore, stratification analysis revealed a significant correlation between rs968697 TC/CC and hepatoblastoma risk for males and clinical stage I+II. The existence of 2-3 protective genotypes was correlated with decreased hepatoblastoma susceptibility in children >= 17 months old, males, and clinical stage I+II cases, when compared to 0-1 protective genotype. Conclusion: To summarize, these results indicated that the HMGA2 gene SNPs exert a weak influence on hepatoblastoma susceptibility. Further validation of the current conclusion with a larger sample size covering multi-ethnic groups is warranted.