A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma
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Chiao-Wen Lin1,2, Ying-Erh Chou3,4, Chia-Ming Yeh4,5, Shun-Fa Yang4,5, Chun-Yi Chuang3,6 and Yu-Fan Liu7,8
1Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
2Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
3School of Medicine, Chung Shan Medical University, Taichung, Taiwan
4Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
5Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
6Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan
7Department of Biomedical Sciences, College of Medicine Sciences and Technology, Chung Shan Medical University, Taichung, Taiwan
8Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan
Yu-Fan Liu, email: [email protected]
Keywords: HMGB1, polymorphism, OSCC, bioinformatics analysis, haplotypes
Received: January 04, 2017 Accepted: February 15, 2017 Published: March 11, 2017
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.
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