Genetic Variations of VEGFA Gene Are Associated With Infiltration of Adjacent Tissues and the Clinical Outcome of Patients With Nasopharyngeal Carcinoma

Abstract

Background/Aim: The aim of the present study was to investigate the clinical significance of 7 single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA), endothelin receptor type A (EDNRA), nibrin (NBS1) and Fas cell surface death receptor (FAS) genes in patients with nasopharyngeal carcinoma (NPC). Patients and Methods: Genomic DNA was extracted from the peripheral blood specimens of 60 patients. Genotyping of 4 VEGFA polymorphisms, namely VEGFA-1154 G/A (rs1570360),-2578 A/C (rs699947),-1498 C/T (rs833061) and +936 C/T (rs3025039), as well as EDNRA SNP p.His323 (rs5333), NBS1 p.E185Q (rs1805794) and FAS-671 A/G (rs1800682) was performed by using Sanger sequencing. Results: The VEGFA +936 CC genotype was more frequent in tumors with bilateral infiltration of pterygoid plates compared to those with ipsilateral (76.9% vs. 69.6%, p=0.008) and no infiltration of pterygoid plates (76.9% vs. 68.8%, p=0.023). VEGFA-2578, VEGFA-1154 and VEGFA +936 were significantly associated with infiltration to the pterygoid processes (p=0.011, p=0.041 and p=0.032, respectively). EDNRA H323H TT genotype was marginally associated with infiltration to the ipsilateral medial pterygoid muscles (p=0.045). A trend towards longer overall survival was observed for VEGFA-2578 CC as compared to AC (HR=0.24, p=0.060). Conclusion: The studied VEGFA SNPs seem to be associated with the local extension of the NPC and maybe with the clinical outcome of this patient group. Nasopharyngeal carcinoma (NPC) is a rare human malignancy with an annual incidence of 0.1-1.1/100,000 people with Caucasian origin in western countries.

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“…In addition, the stability of the VEGFA mRNA is influenced by hypoxia and growth factors via the binding of proteins at AU-rich elements in the 3′-UTR, which also contains a riboswitch that plays a role in the regulation of VEGFA mRNA translation [53,54]. The variability of the VEGFA gene plays a role in the functioning of its product and has been explored in studies of human diseases [55][56][57].…”