Genetic Variants of EGF and VEGF Predict Prognosis of Patients with Advanced Esophageal Squamous Cell Carcinoma

PURPOSE: To investigate the association between genetic polymorphisms of growth factor-related genes and prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: A total of 334 ESCC patients with advanced tumor stages (stages IIB, III and IV) were enrolled in the study. The genotypes of 14 candidate single nucleotide polymorphisms (SNPs) involved in growth factor-related functions were analyzed using iPLEX Gold technology from the genomic DNA of peripheral leukocytes, and were correlated with the clinical outcome of patients. Serum levels of growth factors were examined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The genetic polymorphisms of EGF:rs4444903, EGF:rs2237051 and VEGF:rs2010963 showed significant associations with overall survival (OS) of advanced ESCC patients (A/A+ A/G vs. GG, [HR = 0.77, 95% CI = 0.60–0.99, P = 0.039 for rs4444903; A/G+ G/G vs. A/A, [HR = 0.74, 95% CI = 0.58–0.95, P = 0.019 for rs2237051; G/G+G/C vs. C/C, [HR] inves = 0.69, 95% CI = 0.50–0.95, P = 0.023 for rs2010963). EGFR:rs2227983 and 3 SNPs of PIK3CA also showed borderline significant correlation with OS of advanced ESCC patients (P = 0.058 for rs2227983; P = 0.069, 0.091 and 0.067 for rs6443624, rs7651265 and rs7621329 of PIK3CA respectively). According to cumulative effect analysis of multiple SNPs, patients carrying 4 unfavorable genotypes exhibited more than a 3-fold increased risk of mortality. Finally, both EGF and VEGF expression levels significantly associated with patient mortality. CONCLUSION: The genetic variants and expression levels of EGF and VEGF can serve as prognostic predictors in patients with advanced ESCC, and thus provide more information for optimizing personalized therapies for patients with ESCC.