A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma.

Chiao-Wen Lin,Chia-Ming Yeh,Yu-Fan Liu,Ying-Erh Chou,Shun-Fa Yang,Chun-Yi Chuang

doi:10.18632/oncotarget.16120

Chiao-Wen Lin, Chia-Ming Yeh + Show 4 more

Open Access

https://doi.org/10.18632/oncotarget.16120

Copy DOI

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignancy that has been causally associated with both hereditary and acquired factors. The high mobility group box 1 (HMGB1) gene plays an important role as a DNA chaperone to help maintain nuclear homeostasis. Altered expression of HMGB1 has been implicated in a wide range of pathological processes, including inflammation and cancer. The present study explores the impact of HMGB1 gene polymorphisms, combined with environmental risks regarding susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene, rs1412125, rs2249825, rs1045411, and rs1360485, were evaluated in 1,200 normal controls and 772 patients with OSCC. We found an association between the wild-type allele of rs1045411 and genotypes CT and CT/TT (AOR=0.754, 95% CI=0.582-0.978 and AOR=0.778, 95% CI=0.609-0.995, respectively). Additionally, bioinformatics analysis was used to characterize the functional relevance of these variants for the miRNA-505-5p binding site and transcriptional regulation by the HMGB1 3’-UTR and promoter regions. Moreover, in considering behavioral exposure to environmental carcinogens, the presence of the four HMGB1 SNPs, combined with/without betel quid chewing and smoking showed, profoundly synergistic effects on the risk of OSCC. In conclusion, we present a potential clinical relevance for HMGB1 variants in OSCC, as well as associations between HMGB1 polymorphisms, haplotypes and environmental risk factors. The finding may help in development of optimal therapeutic approaches for OSCC patients.

Highlights

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide, with 599,000 new cases and 325,000 cancer deaths in 2012[1, 2]
A total of 1,972 participants, including 772 OSCC cases and 1,200 controls were recruited to explore the effects of the high mobility group box 1 (HMGB1) gene on OSCC risk
According to the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) in a multiple logistic regression model for HMGB1 polymorphism and OSCC, compared with their corresponding wild-type homozygotes (C/C), only rs1045411 consensus motif of (C/T) or C/T+T/T presented a significant (P

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide, with 599,000 new cases and 325,000 cancer deaths in 2012[1, 2]. OSCC, which accounts for more than 90% of all mouth malignancies and approximately 40% of head and neck tumours has, a high potential for local invasion and lymph node metastasis. Nucleotide change dbSNP (rs number) Molecular consequences ‡ Function prediction. Early-stage OSCCs has a high treatment success rate approximately 70% of patients with progressive disease cannot be successfully treated due to relatively high local and regional recurrence rates [5]. Early detection and clarification of the detailed molecular mechanism of OSCC are urgently needed [6, 7]

Objectives

Methods

Results

Conclusion