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.