Interaction among variant vascular endothelial growth factor (VEGF) and its receptor in relation to prostate cancer risk

BACKGROUND. Prostate cancer (PCa) incidence and mortality are disproportionately high among African-American (AA) men. Its detection and perhaps its disparities could be improved through the identification of genetic susceptibility biomarkers within essential biological pathways. Interactions among highly variant genes, central to angiogenesis, may modulatesusceptibilityforprostate cancer,aspreviousdemonstrated.Thisstudyevaluatesthe interplay among three highly variant genes (i.e., IL-10, TGFbR-1, VEGF), their receptors and their influence on PCa within a case-control study consisting of an under-served population. METHODS. This study evaluated single gene and joint modifying effects on PCa risk in a case-control study comprised of 859 AA men (193 cases and 666 controls) using TaqMan qPCR. Interaction among polymorphic IL-10, TGFbR-1 and VEGF was analyzed using conventional logisticregressionanalysis(LR)models,multi-dimensionalityreduction(MDR)andinteraction entropy graphs. Symbolic modeling allowed validation of gene‐gene interaction findings identified by MDR. RESULTS. No significant single gene effects were demonstrated in relation to PCa risk. However, carriers of the VEGF 2482T allele had a threefold increase in the risk of developing aggressivePCa.ThepresenceofVEGF2482Tcombinedwith VEGFRIVS6 þ54lociwerehighly significant for the risk of PCa based on MDR and symbolic modeling analyses. These findings were substantiated by 1,000-fold cross validation permutation testing (P ¼0.04), respectively.