Five polymorphisms of vascular endothelial growth factor (VEGF) and risk of breast cancer: A meta-analysis involving 16,703 individuals

Associations between five polymorphisms of vascular endothelial growth factor (i.e., VEGF +936C/T, −1154A/G, −2578C/A, −634G/C and −460T/C) and risk of breast cancer have been extensively studied, and the currently available results are inconclusive. Therefore, we performed this meta-analysis to further study the associations. The databases of Pubmed, Embase and CNKI were retrieved up to April 1st, 2010. The pooled ORs and 95% CIs were used to assess the strength of the associations. A total of 10 case-control studies with 8175 cases and 8528 controls were included in this study. The overall results of combined analyses showed that five polymorphisms of VEGF were not associated with risk of breast cancer [ORs (95% CIs): 1.03 (0.84-1.27) for CC vs. TT for +936C/T, 0.95 (0.81-1.12) for AA vs. GG for −1154A/G, 1.01 (0.90-1.14) for CC vs. AA for −2578C/A, 1.02 (0.90-1.16) for GG vs. CC for −634G/C and 0.86 (0.68-1.09) for TT vs. CC for −460T/C]. When subgroup analyses by ethnicity for VEGF +936C/T and −634G/C, the results suggested that +936C/T was not associated with the risk of breast cancer for either Asians [1.40 (0.92-2.13) for CC vs. TT and CC + CT vs. TT: 1.38 (0.91-2.10) for CC + CT vs. TT] or Caucasians [0.93 (0.73-1.19) for CC vs. TT and 0.91 (0.72-1.16) for CC + CT vs. TT], and −634G/C was not associated with the breast cancer for Caucasians [1.07 (0.92-1.24) for GG vs. CC and 1.05 (0.91-1.21) for GG + GC vs. CC]. In addition, when excluding one study, which was out of Hardy-Weinberg equilibrium for VEGF +963C/T and whose controls were from both patients and healthy people, the negative results were also persistent, and ORs (95% CIs) were 1.04 (0.84-1.29) for CC vs. TT, 1.03 (0.83-1.27) for (CC + CT) vs. TT. This meta-analysis suggests that the VEGF +936C/T, −1154A/G, −2578C/A, −634G/C and −460T/C may be not associated with risk of breast cancer development based on the currently available studies, especially for Caucasians. More well designed studies with larger sample size on different ethnicities are needed to further assess the associations.

► The relationships between five polymorphisms of VEGF and breast cancer risk have been explored by a meta-analysis. ► This meta-analysis was based on 10 primary case-control studies, with 8175 cases and 8528 controls. ► The results of this meta-analysis indicated the no associations between five VEGF polymorphisms and breast cancer risk. ► More well designed studies with larger sample size on different ethnicities are needed to further assess the associations.