Impact of HOTAIR Gene Polymorphism and Environmental Risk on Oral Cancer

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Oral squamous cell carcinoma (OSCC) risk and prognosis are influenced by genetic and acquired factors.
• HOX transcript antisense intergenic RNA (HOTAIR) is a key gene regulator implicated in various cancers.
• HOTAIR gene polymorphisms have been associated with cancer predisposition.

Purpose of the Study:

• To investigate the combined effects of HOTAIR gene polymorphisms and environmental factors on oral tumorigenesis.
• To evaluate the association of specific HOTAIR single-nucleotide polymorphisms (SNPs) with OSCC risk and clinical progression.

Main Methods:

• Genotyping of four HOTAIR SNPs (rs920778, rs1899663, rs4759314, rs12427129) in 1,200 controls and 907 OSCC patients.
• Statistical analysis adjusted for smoking, betel quid chewing, and alcohol consumption.
• Subgroup analyses excluding environmental factor exposure and correlation with clinical tumor characteristics.

Main Results:

• rs1899663 polymorphism showed a significant association with increased OSCC risk (aOR=2.227, P=0.012).
• In non-betel quid users, rs920778 polymorphism was linked to higher OSCC susceptibility (OR=1.472, P=0.018 for TC; OR=1.448, P=0.020 for TC+CC).
• Among non-betel quid chewers, rs920778 and rs4759314 correlated with larger tumor size (OR=1.891, P=0.04) and lymph node metastasis (OR=4.140, P=0.001), respectively.
• Functional assessments indicated rs920778 influences HOTAIR expression and epigenetic status.

Conclusions:

• HOTAIR gene polymorphisms, particularly rs1899663 and rs920778, are associated with OSCC risk.
• An interactive effect exists between HOTAIR polymorphisms and betel quid chewing in oral cancer development.
• Specific HOTAIR SNPs may serve as biomarkers for tumor progression in OSCC patients, especially non-betel quid users.