Association of HMGB1 Gene Polymorphisms with Risk of Colorectal Cancer in a Chinese Population

Wang, Jianxin; Yu, Hongwen; Bei, Shao-Sheng; Cui, Zhenhua; Li, Zhiwen; Liu, Zhen-Ji; Lv, Yanfeng

doi:10.12659/msm.896693

Cited by 18 publications

(11 citation statements)

References 31 publications

(33 reference statements)

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“…From RAGE gene, four polymorphisms including rs1800625 (promoter region), rs1800624 (promoter region), rs2070600 (exon 3) and rs184003 (intron 7) were selected. These polymorphisms were widely studied in predisposition to a variety of cancer types, including breast cancer [ 33 ], gastric cancer [ 34 , 35 ], colorectal cancer [ 29 , 36 ], lung cancer [ 37 , 38 ] and so on.…”

Section: Methodsmentioning

confidence: 99%

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: Methodsmentioning

confidence: 99%

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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“…However, the results of our study have demonstrated that the HMGB1 polymorphisms rs1412125, rs1045411, and rs1360485 were associated with prostate cancer disease progression and severity ( Table 3 , Table 4 and Table 5 ), suggesting more consistency of HMGB1 SNPs in the oncogenicity of various cancers. In contrast, we found that the HMGB1 rs2249825 polymorphic variants showed no significant association with prostate cancer susceptibility ( Table 2 ) or the clinical status of prostate cancer, suggesting a difference from colorectal cancer [ 33 ] and cervical cancer [ 47 ]. Besides, our previous study found that urothelial cell carcinoma (UCC) patients who carry at least one T allele of the HMGB1 rs1045411 polymorphism had a lower risk and less invasive disease [ 50 ].…”

Section: Discussionmentioning

confidence: 90%

“…The role of HMGB1 SNPs in cancer risk, disease progression, and tumor development remains controversial. Some studies have associated HMGB1 SNPs with increased cancer risk, disease susceptibility, severity, and progression, or poorer response to treatment [ 22 , 23 , 27 , 31 , 33 , 42 , 46 , 47 , 48 , 49 ]. However, other studies have indicated that the HMGB1 SNPs are associated with a lower risk of cancer and a less invasive disease [ 26 , 50 ], or may even not be associated with the risk of cancer [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, HMGB1 was suggested as a novel target for potential therapeutics since highly expressed HMGB1 was found to be associated with the epithelial-to-mesenchymal transition (EMT) and the overexpression of MMP-1, MMP-3, and MMP-10 via the RAGE/NF-κB signaling pathways, facilitating prostate cancer metastasis [ 1 , 16 , 17 , 18 , 19 , 20 ]. Furthermore, polymorphisms of HMGB1 have been associated with many cancers, including oral squamous cell carcinoma (OSCC) [ 21 , 22 ], lung cancer [ 23 , 24 , 25 , 26 ], breast cancer [ 27 , 28 , 29 ], gastric cancer [ 30 ], hepatocellular carcinoma (HCC) [ 31 , 32 ], and colorectal cancer (CRC) [ 33 ], and it was suggested that the SNPs of HMGB1 may provide a potential biomarker for predicting cancer risk, tumor development, or chemotherapy responses [ 21 , 25 , 27 , 31 ]. However, the impact of HMGB1 polymorphisms on prostate cancer susceptibility and clinicopathologic characteristics has remained uninvestigated.…”

Section: Introductionmentioning

confidence: 99%

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The Impact of HMGB1 Polymorphisms on Prostate Cancer Progression and Clinicopathological Characteristics

Chou

Yang

Lin

et al. 2020

IJERPH

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Prostate cancer is one of the major cancers of the genitourinary tract. High-mobility group box 1 (HMGB1) was suggested as a promising therapeutic target for prostate cancer. In this study, we aim to elucidate the associations of HMGB1 single nucleotide polymorphisms (SNPs) with prostate cancer susceptibility and clinicopathological characteristics. The HMGB1 SNPs rs1412125, rs2249825, rs1045411, and rs1360485 in 579 prostate cancer patients and 579 cancer-free controls were analyzed with real-time polymerase chain reactions (real-time PCR). All of the data were evaluated with SAS statistical software. Our results showed that the HMGB1 rs1045411 T allele genotype was significantly associated with advanced pathologic T stage (odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.021–2.012; p = 0.037) and pathologic N1 stage (OR = 2.091, 95% CI = 1.160–3.767; p = 0.012), and the rs1360485 polymorphic CT + TT genotype was associated with pathologic Gleason grade group (4 + 5) (OR = 1.583, 95% CI = 1.017–2.462; p = 0.041), pathologic T stage (3 + 4) (OR = 1.482, 95% CI = 1.061–2.070; p = 0.021), and pathologic N1 stage (OR = 2.131, 95% CI = 1.178–3.852; p = 0.011) compared with their wild-type carriers. In conclusion, our results revealed that the HMGB1 SNPs were associated with the clinical status of prostate cancer. The HMGB1 SNPs may have the potential to predict prostate cancer disease progression.

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“…The full texts of 19 articles were reviewed, and an additional 9 articles were excluded (with 8 articles excluded for not providing usable data and 1 article excluded due to the duplication of the same article in different languages); thus, 10 studies remained for further review. One study 24 whose distribution of genotype deviated from Hardy-Weinberg equilibrium (HWE) ( p HWE < 0.05) in the control was also included in this study but was excluded from the sensitivity analysis.…”

Section: Resultsmentioning

confidence: 99%

Association of Polymorphism rs1045411 in the HMGB1 Gene with Cancer Risk: Evidence from a Meta-analysis

Qing¹,

Tao²,

Xu³

2021

Int. J. Med. Sci.

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The high-mobility group box protein 1 (HMGB1) rs1045411 polymorphism has been demonstrated to be associated with cancer risk in some studies. However, the results regarding this topic are inconsistent. A meta-analysis was applied to elucidate the association between the HMGB1 rs1045411 polymorphism and cancer risk. Ten relevant studies were subjected to our analysis, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. In total, of 3,918 cases and 5,296 controls were included in this study. The pooled ORs were calculated using a random-effects or fixed-effects model according to the heterogeneity. The pooled results revealed that TT genotype was significantly related to increased cancer risk in the comparisons of TT vs. CC+TC (OR=1.35; 95% CI: 1.09-1.67; p =0.005). Though no statistical significance was achieved between HMGB1 rs1045411 polymorphism and cancer risk in other four genetic models (T vs. C: OR=1.08, 95% CI 0.90-1.30; TC vs. CC: OR=1.01, 95% CI 0.82-1.24; CC vs. TC+TT: OR=0.95, 95% CI 0.77-1.18; TT vs. CC: OR=1.42; 95% CI 0.98-2.05), a trend of increased risk could be drawn. In the subgroup analysis by type of malignancy and ethnicity, no obvious difference was found in the tumour risk regarding the HMGB1 rs1045411 polymorphism amongst the cancer types except for breast cancer (OR=1.94; 95% CI: 1.05-3.59; p =0.03) and hepatocellular carcinoma (OR=1.82; 95% CI: 1.15-2.88; p =0.01), while rs1045411 polymorphism was positively associated with risks of cancer amongst Hans (OR=1.37; 95% CI: 1.11-1.69; p =0.004) rather than Caucasians (OR=0.89; 95% CI: 0.26-3.02; p =0.01). These results suggest that the HMGB1 rs1045411 polymorphism might be associated with increased cancer risk.

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Association of HMGB1 Gene Polymorphisms with Risk of Colorectal Cancer in a Chinese Population

Cited by 18 publications

References 31 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

The Impact of HMGB1 Polymorphisms on Prostate Cancer Progression and Clinicopathological Characteristics

Association of Polymorphism rs1045411 in the HMGB1 Gene with Cancer Risk: Evidence from a Meta-analysis

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