Genetic Variation in the Vascular Endothelial Growth Factor (VEGFA) Gene at rs13207351 Is Associated with Overall Survival of Patients with Head and Neck Cancer

SIMPLE SUMMARY: Angiogenesis and apoptosis play a pivotal role in the pathogenesis and clinical course not only of nasopharyngeal cancer (NPC), but also of other subgroups of head and neck cancer (HNC), such as laryngeal cancer. Thus, the aim of this study was to investigate the clinical significance of genetic polymorphisms in four pivotal angiogenesis- and apoptosis-related genes (VEGFA, FAS, EDNRA and NBS1) in HNC patients. Thirty-four genetic variants located in the studied genes were assessed. Two of them (VEGFA rs13207351 and FAS rs2234768) were associated with overall survival for patients with laryngeal cancer and NPC, respectively, with VEGFA rs13207351 showing the most promise for its prognostic value in the subgroup of laryngeal cancer patients. This study suggests that genetic variations in angiogenesis- and apoptosis-related genes may be useful in the management of HNC patients. ABSTRACT: Head and neck cancer (HNC) is a significantly heterogeneous disease and includes malignancies arising from different anatomical sites, such as nasopharyngeal cancer (NPC) and laryngeal cancer (LC). In the current study, polymorphisms located in angiogenesis- and apoptosis-related genes (VEGFA, FAS, EDNRA and NBS1) were evaluated regarding their clinical significance in HNC patients. In total, 333 HNC patients were enrolled in this study and 34 variants located on the aforementioned genes were genotyped via Sanger sequencing. LC patients, homozygous A for VEGFA rs13207351, had shorter overall survival (OS) as opposed to homozygous G (Hazard ratio (HR) = 2.06, Wald’s p = 0.017) upon adjustment for age, disease stage, and surgery. Following the dominant model, LC patients carrying the A allele had a marginally significantly higher risk for death (HR = 1.72, p = 0.059). NPC patients heterozygous (CT) for FAS rs2234768 had a marginal but significantly higher risk of death compared to those with homozygosity for the T allele (HR = 2.22, p = 0.056). In conclusion, rs13207351 (VEGFA) and rs2234768 (FAS) polymorphisms seem to have prognostic significance in HNC, with VEGFA rs13207351 showing the most promise in this subgroup of LC patients.