Positive association of the vascular endothelial growth factor-A +405 GG genotype and poor survival in stage I-II gastric cancer in the Northern Chinese population.

The vascular endothelial growth factor-A (VEGF-A) plays an important role in the angiogenesis and prognosis for gastric cancer. In addition, several single-nucleotide polymorphisms (SNPs) in VEGF-A have been shown to affect gene expression and process of angiogenesis. The present study evaluated the correlations between SNPs in VEGF-A and gastric cancer survival. Formalin-fixed paraffin-embedded tissues of 404 gastric cancer patients and blood samples from 404 controls were included in the study. The SNPs -460T/C (rs833061), +405G/C (rs2101963), -7C/T (rs25648) and +936C/T (rs3025039) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. We showed patients carrying the +405GG genotype had significantly worse survival in the N0 (lymph-node negative), N0L0 (lymph-node negative and lymphovascular-invasion negative) and TNM stage I-II subgroups (P = 0.021, P = 0.007 and P = 0.017, respectively). In addition, haplotype -460T/+405G/-7C and -460C/+405G/-7C carriers showed poor survival in the N0, N0L0 and TNM stage I-II subgroups (P = 0.004, P = 0.030 and P = 0.009 for TGC; P = 0.033, P = 0.049 and P = 0.011 for CGC). Overall, the +405 GG genotype or TGC and CGC haplotypes were correlated with poor survival in TNM stage I-II gastric cancer patients. The +405G/C polymorphism of VEGF-A could be used as a biomarker for molecular staging in stage I-II gastric cancer in Northern China.