Association between VEGF–460T/C gene polymorphism and clinical outcomes of nasopharyngeal carcinoma treated with intensity-modulated radiation therapy

Junyin Tan,* Li Jiang,* Xiaowei Cheng, Chunlin Wang, Jingshan Chen, Xiaoqing Huang, Peng Xie, Dongmei Xia, Rensheng Wang, Yong Zhang

Department of Radiotherapy, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China

*These authors contributed equally to this work

Abstract: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a critical role in the development, metastasis, and recurrence of tumors. This study aims to determine the correlation of single-nucleotide polymorphisms in the VEGF gene with the prognosis of nasopharyngeal carcinoma (NPC). The VEGF –460T/C gene polymorphisms in the genomic DNA of the blood samples of 338 patients with NPC were investigated through polymerase chain reaction and direct DNA sequencing. Results showed a significant association between the –460C-allele carriers and the aggressive forms of NPC as defined by stages N2–3 (odds ratio =1.820, 95% confidence interval [CI]: 1.118–2.962, P=0.015). Furthermore, the VEGF –460T/C polymorphism was significantly associated with 3-year overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) (T/C + C/C vs T/T: 3-year OS 78.8% vs 95.1%, P=0.003; 3-year DMFS 80.2% vs 90.6%, P=0.036; 3-year PFS 73.9% vs 86.7%, P=0.042) but was not associated with the local recurrence-free survival (LRFS) of the patients. The multivariate analysis indicated that the VEGF –460C-allele carrier was an independent significant prognostic factor for OS (hazard ratio [HR] 4.096, 95% CI: 1.333–12.591, P=0.014). N classification was an independent significant prognostic factor for DMFS in patients with locoregionally advanced NPC (HR 3.674, 95% CI: 1.144–11.792, P=0.029). However, neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) was not superior to CCRT alone in terms of the 3-year OS, LRFS, DMFS, and PFS of patients with VEGF –460T/C polymorphism. In conclusion, the VEGF –460T/C gene polymorphism may negatively affect the clinical outcomes of patients with NPC and may be considered a potential prognostic factor for this disease.

Keywords: vascular endothelial growth factor, gene polymorphism, nasopharyngeal carcinoma, clinical outcomes