Contribution of MYD88 Single Nucleotide Polymorphisms to Hypopharyngeal Squamous Cell Carcinoma Development and Progression

Abstract

Background and Objectives Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare but aggressive head and neck malignancy, characterized by poor prognosis and low survival rates. Despite advances in treatment, the molecular mechanisms underlying HSCC development and progression remain misunderstood. The MYD88 gene, which encodes a crucial adaptor protein in innate immune signaling pathways, and its dysregulation have been linked to oncogenesis across many tumor types. However, the role of MYD88 genetic variants in HSCC has not been thoroughly investigated. Material and Method This retrospective case–control study was conducted in the Lithuanian University of Health Sciences, Department of Otorhinolaryngology, between 2017 and 2024, including 79 male patients with histologically confirmed HSCC and 220 healthy male controls. Clinical and pathological data were collected from medical records. Genomic DNA was extracted from peripheral blood samples, and selected MYD88 polymorphisms (rs7744 and rs6853) were genotyped using real-time PCR with TaqMan probes in the Oncology Research Laboratory, Institute of Oncology. Statistical analyses were performed using SPSS (version 30.0). Results The MYD88 rs7744 polymorphism was significantly associated with distant metastasis. Carriers of the GG genotype had a markedly increased risk compared to AA genotype carriers (OR = 28.46, 95% CI: 1.85–438.82, p = 0.016). No significant associations were observed between MYD88 polymorphisms and HSCC susceptibility, relapse-free survival, or overall survival. Additionally, rs6853 showed no association with clinicopathological features. Conclusions and Recommendations The MYD88 rs7744 variant might play a role in tumor progression, specifically regarding distant metastasis, rather than in susceptibility to HSCC.