title: A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk.
abstract: 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.
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Qi
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Chuanhua
authors.initials: C
authors.lastname: Yang
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wei
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Mi
authors.affiliation: Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D024243:HMGB1 Protein / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*; D012307:Risk Factors
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000067759:Receptor for Advanced Glycation End Products
keywords: HMGB1/RAGE axis; genetic susceptibility; haplotype; hepatocellular carcinoma; polymorphism