Pharmacogenomics and Personalized Medicine (Feb 2020)
HMGA2 Polymorphisms and Hepatoblastoma Susceptibility: A Five-Center Case-Control Study
Abstract
Li Li, 1,* Zhenjian Zhuo, 2,* Zhen Yang, 1, 3,* Jinhong Zhu, 4 Xiaoli He, 1 Zhonghua Yang, 5 Jiao Zhang, 6 Yijuan Xin, 7 Jing He, 2 Tiesong Zhang 1 1Kunming Key Laboratory of Children’s Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics Research, Kunming Children’s Hospital, Kunming, Yunnan, 650228, People’s Republic of China; 2Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, People’s Republic of China; 3Department of Oncology, Kunming Children’s Hospital, Kunming 650228, Yunnan, People’s Republic of China; 4Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, People’s Republic of China; 5Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, People’s Republic of China; 6Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, People’s Republic of China; 7Clinical Laboratory Medicine Center of PLA, Xijing Hospital, Air Force Medical University, Xi’an 710032, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tiesong ZhangKunming Key Laboratory of Children’s Infection and Immunity, Yunnan Key Laboratory of Children’s Major Disease Research, Yunnan Institute of Pediatrics Research, Kunming Children’s Hospital, 288 Qianxing Road, Kunming 650228, Yunnan, People’s Republic of ChinaTel/Fax +86 – 8713169969Email [email protected] HeDepartment of Pediatric, Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou 510623, Guangdong, People’s Republic of ChinaTel/Fax +86 2038076560Email [email protected]: 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% CI=0.54– 0.98, P=0.035). Notably, participants carrying 2– 3 favorable genotypes had reduced hepatoblastoma risk (adjusted OR=0.71, 95% CI=0.52– 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.Keywords: hepatoblastoma, HMGA2, polymorphism, susceptibility
