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Interaction among variant vascular endothelial growth factor (VEGF) and its receptor in relation to prostate cancer risk
Author(s) -
VanCleave Tiva T.,
Moore Jason H.,
Benford Marnita L.,
Brock Guy N.,
Kalbfleisch Ted,
Baumgartner Richard N.,
Lillard James W.,
Kittles Rick A.,
Kidd La Creis R.
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21067
Subject(s) - prostate cancer , multifactor dimensionality reduction , population , oncology , biology , vascular endothelial growth factor , angiogenesis , medicine , logistic regression , gene , genetics , cancer research , cancer , single nucleotide polymorphism , vegf receptors , genotype , environmental health
Abstract 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 modulate susceptibility for prostate cancer, as previous demonstrated. This study evaluates the interplay among three highly variant genes (i.e., IL‐10, TGFβR‐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, TGFβR‐1 and VEGF was analyzed using conventional logistic regression analysis (LR) models, multi‐dimensionality reduction (MDR) and interaction 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 aggressive PCa. The presence of VEGF 2482T combined with VEGFR IVS6 + 54 loci were highly 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 = 0.04), respectively. CONCLUSION These findings suggest the inheritance of VEGF and VEGFR IVS6 + 54 sequence variants may jointly modify PCa susceptibility through their influence on angiogenesis. Larger sub‐population studies are needed to validate these findings and evaluate whether the VEGF‐VEGR axis may serve as predictors of disease prognosis and ultimately clinical response to available treatment strategies. Prostate 70: 341–352, 2010. © 2009 Wiley‐Liss, Inc.