Clinical Research Papers:

A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk

Dan Wang, Xiaoying Qi, Fang Liu, Chuanhua Yang, Wenguo Jiang, Xiaodan Wei, Xuri Li, Jia Mi and Geng Tian _

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Oncotarget. 2017; 8:50109-50116. https://doi.org/10.18632/oncotarget.15202

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Dan Wang1,*, Xiaoying Qi1, Fang Liu1,*, Chuanhua Yang1, Wenguo Jiang1, Xiaodan Wei1, Xuri Li1, Jia Mi1 and Geng Tian1

1 Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China

* The first two authors have contributed equally to this work

Correspondence to:

Geng Tian, email:

Jia Mi, email:

Xuri Li, email:

Keywords: hepatocellular carcinoma; HMGB1/RAGE axis; polymorphism; genetic susceptibility; haplotype

Received: December 22, 2016 Accepted: January 25, 2017 Published: February 08, 2017


Based on 540 hepatocellular carcinoma patients and 540 age- and gender-matched controls, we tested the hypothesis that high mobility group protein box1 (HMGB1) and the receptor for advanced glycation end products (RAGE) genes are two potential candidate susceptibility genes for hepatocellular carcinoma in a multicenter hospital-based case-control analysis. The genotypes of seven widely-studied polymorphisms were determined, and their distributions respected the Hardy-Weinberg equilibrium. The mutant alleles of two polymorphisms, rs1045411 in HMGB1 gene and rs2070600 in RAGE gene, had significantly higher frequencies in patients than in controls (P < 0.001), with the power to detect this significance of being over 99.9%. Moreover, the above two polymorphisms increased the risk of developing hepatocellular carcinoma significantly, particularly for rs2070600 under the additive (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.34-2.32; P < 0.001) and dominant (OR = 1.75; 95% CI: 1.23-2.50; P = 0.002) models after adjusting for body mass index, smoking and drinking. Haplotype analysis showed that the T-C-T haplotype (rs1045411-rs2249825-rs1415125) in HMGB1 gene was associated with a 2.47-fold (95% CI: 1.41-4.34; P = 0.002) increased risk of hepatocellular carcinoma compared with the commonest C-C-T haplotype after adjustment. In RAGE gene, the T-T-A-G (rs1800625-rs1800624-rs2070600-rs184003) (adjusted OR; 95% CI; P: 1.75; 1.02-3.03; 0.045) and T-T-A-T (adjusted OR; 95% CI; P: 1.95; 1.01-3.76; 0.048) haplotypes were associated with a marginally increased risk of hepatocellular carcinoma compared with the commonest T-T-G-G haplotype. In summary, we identified two risk-associated polymorphisms (rs1045411 and rs2070600), and more importantly a joint impact of seven polymorphisms from the HMGB1/RAGE axis in susceptibility to hepatocellular carcinoma.

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