Impact of TNF-α (rs1800629) and TNF-β (rs2229094) Genetic Variants on Laryngeal squamous cell carcinoma Development and Staging

Introduction Laryngeal squamous cell carcinoma (LSCC) is the most common form of laryngeal cancer, arising from epithelial malignancy [1]. Despite advancements in treatment techniques, survival rates are still seriously threatened by metastasis and recurrence [2]. Understanding LSCC’s molecular mechanisms and identifying biomarkers are crucial for improving diagnosis and prognosis. Tumor necrosis factor (TNF) superfamily members play essential roles in a healthy immune system [3]. TNF-α can act as a tumor-promoting cytokine [4]. It can contribute to developing neoplasms in several ways, including cellular transformation, proliferation, angiogenesis, migration, and invasion [5]. TNF-β responds to immune and inflammatory reactions and plays a role in cancer pathogenesis [6]. Genetic variations in the TNF-α and -β may alter cytokine expression, affecting cancer susceptibility and progression. Aim The study aimed to determine the association between the LSCC occurrence, staging, and TNF-α and -β gene variants. Methods A total of 190 patients with LSCC and 190 healthy individuals participated in the study. Venous blood samples were collected, and DNA was extracted using the salting-out method. Genotyping of TNF-α and -β variants (rs2229094 and rs1800629) was carried out through real-time polymerase chain reaction (RT-PCR). Statistical analysis was conducted using IBM SPSS Statistics 30.0 software, and a statistically significant difference was found when p < 0.025 after Bonferroni correction. Results Results showed that according to the additive model, each C allele of TNF-β rs2229094 increases the odds of LSCC development by 1.6-fold (p = 0.008), while each A allele of TNFα rs1800629 decreases these odds by 1.6-fold (p = 0.023). When dividing LSCC patients by disease stage, we found that each C allele of rs2229094 increases the odds of early-stage LSCC occurrence by 1.8-fold under the additive model (p = 0.016). Conclusions Our findings suggest that TNF-β rs2229094 and TNF-α rs1800629 genes’ variants influence LSCC susceptibility, with the C allele of rs2229094 increasing risk and the A allele of rs1800629 having a protective effect.