Variant alleles of VEGF and risk of esophageal cancer and lymph node metastasis.

CONDENSED ABSTRACT: The variant alleles of the functional polymorphisms, VEGF -2578 C > A, -1498 T > C and +936 C > T, were not associated with risk of esophageal cancer and lymph node metastasis. Compared with the most common haplotype, C-2578T-1498C+936, the A-2578C-1498C+936 haplotype was associated with a borderline significantly increased risk of esophageal cancer. C-2578C-1498C+936 and A-2578T-1498T+936 haplotypes were associated with significantly increased risk of esophageal cancer. Vascular endothelial growth factor (VEGF) is a potent stimulator for angiogenesis. It has been implicated in the growth and metastasis of esophageal cancer. Three functional single nucleotide polymorphisms (SNPs) of VEGF (-2578 C > A, -1498 T > C and +936 C > T) are known to be related to VEGF expression. We conducted a case-control study to evaluate the effects of these three functional SNPs on the development of esophageal cancer and lymph node metastasis. A total of 497 cases and 380 controls were analyzed. Genotypes were determined by matrix assisted laser desorption/ionization time-of-flight mass spectrometry and direct sequence methods. The variant alleles of the functional polymorphisms VEGF -2578 C > A, -1498 T > C and +936 C > T SNPs were not associated with esophageal cancer risk. These VEGF genotypes were not associated with the risk of esophageal cancer after stratification. Furthermore, no association was observed between VEGF -2578 C > A, -1498 T > C and +936 C > T polymorphisms and lymph node metastasis. Compared with the most common haplotype C-2578T-1498C+936, the A-2578C-1498C+936 haplotype was associated with a borderline significantly increased risk of esophageal cancer. C-2578C-1498C+936 and A-2578T-1498T+936 haplotypes were associated with significantly increased risk of esophageal cancer. Variants in the functional polymorphisms of VEGF may not contribute to esophageal cancer and lymph node metastasis susceptibility. VEGF A-2578C-1498C+936, C-2578C-1498C+936 and A-2578T-1498T+936 haplotypes may be associated with increased risk of esophageal cancer. However, our results were obtained with a limited sample size and therefore this is a preliminary conclusion. Validation by a larger study with more diverse ethnic populations is needed.