TNF variants influence metastasis in laryngeal squamous cell carcinoma

Background. Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumour of the respiratory tract, after lung cancer. Despite improved molecular and clinical knowledge, the survival rate of patients with LSCC remains low. It is known that the development of solid tumours is regulated by inflammatory processes, including angiogenesis. Tumour development is facilitated by mast cells that accumulate near blood vessels and secrete mediators that promote angiogenesis and suppress the immune response: vascular endothelial growth factor A, histamine, tumour necrosis factor (TNF), and interleukins. To date, the association of TNF variants involved in angiogenesis with metastasis to the neck lymph nodes in LSCC has not been studied. Aim. The study aimed to determine the association between the LSCC metastasis and TNF variants. Methods. A total of 190 patients with LSCC and 190 healthy individuals were enrolled in the study. DNA was isolated from the venous blood by the salting out method. Genotyping of TNF (rs361525 and rs1800629) variants was performed by real-time polymerase chain reaction (RT-PCR). Statistical data analysis was conducted using the IBM SPSS Statistics 30.0.0.0 software. Results. We determined that the distribution of genotypes and alleles does not differ statistically significantly in LSCC with and without metastasis to the neck lymph nodes compared to the control group. In binomial logistic regression analysis, the results showed that each A allele of TNF rs1800629 reduces the odds of developing non-metastasised LSCC by 1.7-fold under the additive model (OR = 0.579, 95% CI: 0.361–0.927, p = 0.023). The AG genotype and AG+GG genotypes of rs1800629 decrease these odds by 1.9-fold under the codominant and dominant models, respectively (OR = 0.538, 95% CI: 0.316–0.914, p = 0.022 and OR = 0.537, 95% CI: 0.321–0.899, p = 0.018, respectively), while under the overdominant model, the AG genotype decreases these odds by 1.8-fold (OR = 0.545, 95% CI: 0.321–0.926, p = 0.025). Analysis of TNF rs361525 did not reveal any statistically significant results. Conclusion. Our study suggests that the TNF rs1800629 variant may be protective in LSCC metastasis to the neck lymph nodes.