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

Abstract

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.

• Esophageal cancer
• lymph node metastasis
• molecular epidemiology
• polymorphisms
• VEGF

Delcaration of interest

Grant support: This study was supported in part by National Natural Science Foundation of China (81370001, 81371927, 81101889, 81000028), Jiangsu Province Natural Science Foundation (BK2010333, BK2011481), Social Development Foundation of Zhenjiang (SH2010017), Changzhou Young Talents and Science-Technology Foundation of Health Bureau (QN201102), Affiliated People’s Hospital of Jiangsu University fund (Y200913) and Jiangsu University Clinical Medicine Science and Technology Development fund (JLY20120004).

None of the authors have any conflicts of interest or disclosures.