Vascular endothelial growth factor A (VEGFA) promoter rs2010963 polymorphism and cancer risk: An updated meta-analysis and trial sequential analysis

Abstract

ObjectivesPrevious observational studies evaluating the relationship of VEGFA rs2010963 polymorphism with cancer risk reported inconsistent outcomes. We conducted this meta-analysis to confirm a firm correlation of rs2010963 with overall cancers. Materials and methodsA total of 70 eligible studies, including 25,245 cancer patients and 28,219 controls, were retrieved from online databases and included studies that analyzed odds ratio (OR) with 95% confidence intervals. ResultsIn the overall cancers and population, no association between VEGFA rs2010963 and cancer was found. We observed a statistically significant association (p < 0.05) of rs2010963 with increased cancer risk in the African population (codominant 1: OR = 1.44, dominant model: OR = 1.41, allele model: OR = 1.24). Stratification by cancer types showed significant association with urogenital cancer risk under codominant 1 (OR = 1.22), codominant 2 (OR = 1.55), codominant 3 (OR = 1.24), dominant (OR = 1.29), recessive (OR = 1.36), and allele model (OR = 1.24). In renal cell cancer, four genetic models depicted significant correlation, namely codominant 1 (OR = 1.28), codominant 2 (OR = 1.68), dominant (OR = 1.38), and allele model (OR = 1.29). For osteosarcoma, codominant 3 (OR = 0.81) and the overdominant model showed significant association (OR = 1.16). Three genetic models showed a protective effect in thyroid cancer, including codominant 2, recessive, and allele models (OR = 0.48, 0.59, and 0.68, respectively). Only the recessive model in Asian breast cancer patients (OR = 1.16) and codominant 3 and recessive model in mixed patients (OR = 1.43 and 1.39) showed an association.In the overall cancers and population, no association between VEGFA rs2010963 and cancer was found. ConclusionsThe present meta-analysis indicates that VEGFA rs2010963 polymorphism is associated with susceptibility to cancer, especially in African population. Stratified analysis suggests that rs2010963 is also associated with osteosarcoma, urogenital, renal, thyroid, and breast cancer. Trial sequential analysis also validated our findings.