Effects of <i>HMGB1</i> Polymorphisms on the Susceptibility and Progression of Hepatocellular Carcinoma

Wang, Bin; Yeh, Chao‐Bin; Lein, Ming-Yu; Su, Chen-Ming; Yang, Shun‐Fa; Liu, Yu-Fan; Tang, Chih‐Hsin

doi:10.7150/ijms.14877

Cited by 30 publications

(32 citation statements)

References 35 publications

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“…So far the physiological significance of rs1045411 is uncertain, and the location of this polymorphism could suggest a role in mRNA stability as microRNAs can bind the 3'-untranslated regions of mRNA transcripts and inhibit gene expression at the posttranscriptional level. Moreover, in the present study, the mutant allele of rs1045411 was associated with a significantly increased risk of hepatocellualr carcinoma, while another study in a Taiwan population found that carriers of this mutant allele had a lower risk [ 25 ], likely due to differences in lifestyles, diets or study power. On the other hand, the polymorphism rs2070600 is non-synonymous (Gly82Ser) in the exon 3 of RAGE gene, and the association of this polymorphism was significant with a wide range of cancer types, including lung cancer [ 26 ], breast cancer [ 27 ], ovarian cancer [ 28 ] and colorectal cancer [ 29 ].…”

Section: Discussionmentioning

confidence: 52%

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

Wang

Liu

et al. 2017

Oncotarget

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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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Section: Discussionmentioning

confidence: 52%

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

Wang

Liu

et al. 2017

Oncotarget

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“…Wang et al [30] indicated that HCC patients carrying at least one C allele at rs1412125 showed a low risk of distant metastasis. Supic et al [29] revealed that rs2249825 and rs3742305 polymorphisms might be associated with OSCC survival outcomes.…”

Section: Discussionmentioning

confidence: 99%

No association between HMGB1 polymorphisms and cancer risk: evidence from a meta-analysis

Liang

Yang

et al. 2018

Bioscience Reports

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The aim of the present study was to determine whether High mobility group box 1 (HMGB1) polymorphism was associated with cancer susceptibility. PubMed, Embase, and ISI Web of Science were extensively searched without language restriction. Data were extracted using a standardized data collection sheet after two reviewers scanned studies independently. The association between HMGB1 polymorphism and cancer risks was indicated as odds ratio (OR) along with its related 95% confidence interval (95%CI). Meta-analysis was conducted via RevMan 5.3 software. A total of ten studies comprising 4530 cases and 5167 controls were included in our study. Meta-analysis revealed no statistical association between rs1045411, rs1360485, rs1412125, or rs2249825 polymorphisms in HMGB1 gene and risk of cancer, either did subgroup analysis of rs1045411 stratified by cancer types and ethnic groups. Our results revealed no statistical association between current four polymorphism loci and cancer risks, suggesting that the attempt of applying HMGB1 variants as a therapeutic target or a prognosis predictor might still require a second thought. However, HMGB1 is deemed to play pleiotropic roles in cancers, we strongly call for large-scale studies with high evidence level to uncover the exact relationship between HMGB1 gene variants and cancer progression.

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“…Accumulating evidence suggests an association between SNPs in certain genes and HCC susceptibility[81]. GWAS have emerged as a new approach for identifying less penetrant cancer susceptibility alleles that might be associated with the initiation and progression of cancer.…”

Section: Snpsmentioning

confidence: 99%

Genetic alterations in hepatocellular carcinoma: An update

Niu¹,

Niu²,

Wang³

2016

WJG

137

108

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.

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Effects of HMGB1 Polymorphisms on the Susceptibility and Progression of Hepatocellular Carcinoma

Cited by 30 publications

References 35 publications

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

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

No association between HMGB1 polymorphisms and cancer risk: evidence from a meta-analysis

Genetic alterations in hepatocellular carcinoma: An update

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