Significance of HEY2 gene single nucleotide polymorphisms in the development of laryngeal and hypopharyngeal squamous cell carcinoma

Introduction Head and neck cancer is the third most common cancer worldwide, and despite the advances in treatment, the mortality remains high (1). Identifying genetic factors that contribute to disease pathogenesis and patient survival remains essential. HEY2 gene promotes epithelial-mesenchymal transition, a process linked with metastasis formation which is the leading cause of mortality in cancer patients. HEY2 has shown to have prooncogenic role in studies with hepatocellular carcinoma, non-small cell lung cancer and ovarian cancer (2-4). However, there are no studies on HEY2 significance in laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HSCC) development. Aim To evaluate the role of selected HEY2 gene polymorphisms in the development, differentiation, and risk of metastasis of LSCC and HSCC. Methods A total of 172 men with LSCC and 79 men with HSCC were enrolled in this retrospective case-control study, with a control group of 220 healthy men. Women were excluded from this study due to much higher prevalence of LSCC and HSCC in men and limited amount of cases yearly (5). Genomic DNA was extracted from peripheral venous blood samples collected from all individuals. Genotyping of selected HEY2 rs3734637 and rs6940469 polymorphisms was performed using real-time PCR with TaqMan probes. Results Patients with the HEY2 rs3734637 GG genotype had reduced odds of LSCC development compared to those with the TT genotype (OR = 0.545, 95% CI: 0.303–0.980, p = 0.043). This association was also significant in the allelic model, where T allele carriers of HEY2 rs3734637 had a 1.878-fold increased risk of LSCC development compared to non-carriers (OR = 1.878, 95% CI: 1.128–3.126, p = 0.015). Conclusions HEY2 rs3734637 polymorphism TT genotype was associated with increased odds of developing LSCC. There was no statistically significant association between the investigated polymorphisms and the pathomorphological features of HSCC tumors.