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

Abstract

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.

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

“…Compared with the former meta-analysis conducted by Kumari T et al 8 , this study have obtained clear conclusions that rs1045411 polymorphism increased cancer risk in some genetic models, especially in the comparison of TT vs. CC+TC while statistical significance was not achieved in any genetic model for all polymorphisms studied by Li XY et al 7 , probably because more studies with larger sample size were included in this meta-analysis and the number of subjects studied was high. Subgroup analysis was also performed by the type of malignancy and ethnicity stratification in the current study, however, no obvious differences were found in the tumour risks in the HMGB1 rs1045411 polymorphism amongst the cancer types except for breast cancer and hepatocellular carcinoma.…”

“…HMGB1 is a tumour-related gene 28 , and its overexpression of HMGB1 is associated with the hallmarks of cancer 29 , such as unlimited replicative potential, ability to develop blood vessels, evasion of programmed cell death, self-sufficiency in growth signals, insensitivity to inhibitors of growth, inflammation, tissue invasion and metastasis 30 . Because the HMGB1 rs1045411 polymorphism is closely correlated with altered binding of miR-505-5P in the 3'-UTR of mRNA transcripts, HMGB1 gene polymorphisms could emerge as a crucial player in cancer development through a post-transcriptional mechanism 7 , 25 . Furthermore, since the rs1045411 polymorphism resides in the 3'-flanking regions, suggesting a role in mRNA stability as miRNAs can bind the 3'-UTR regions of mRNA transcripts and inhibit HMGB1 expression at the post-transcriptional level 25 .…”

“…By genotyping single-nucleotide polymorphisms (SNPs), the distribution frequency of SNPs among cases and controls can be compared 5 , 6 . Some reports have shown an association between the SNPs rs1045411 and cancer risk; however, the results are controversial 7 , 8 .…”

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

“…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 ]. Of note, no information on HMGB1 polymorphisms and prostate cancer risk was mentioned or discussed in the meta-analysis conducted by Li et al [ 51 ], so the correlations of HMGB1 SNPs with prostate cancer risk and disease progression remain uncertain.…”

“…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 ]. Of note, no information on HMGB1 polymorphisms and prostate cancer risk was mentioned or discussed in the meta-analysis conducted by Li et al [ 51 ], so the correlations of HMGB1 SNPs with prostate cancer risk and disease progression remain uncertain. We found no statistically significant association between the HMGB1 polymorphic variants and prostate cancer patients, implying that the direct impact of HMGB1 SNPs on prostate cancer susceptibility might be limited ( Table 2 ).…”