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

Tiva T. Vancleave, Jason H. Moore, Marnita L. Benford, Guy N. Brock, Ted Kalbfleisch, Richard N. Baumgartner, James W. Lillard, Rick A Kittles, La Creis R Kidd

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)341-352
Number of pages12
JournalProstate
Volume70
Issue number4
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Prostatic Neoplasms
Vascular Endothelial Growth Factor A
Genes
African Americans
Interleukin-10
Case-Control Studies
Vascular Endothelial Growth Factor Receptor-1
Entropy
Genetic Predisposition to Disease
Biomarkers
Logistic Models
Alleles
Regression Analysis
Mortality
Incidence
Population

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Vancleave, T. T., Moore, J. H., Benford, M. L., Brock, G. N., Kalbfleisch, T., Baumgartner, R. N., ... Kidd, L. C. R. (2010). Interaction among variant vascular endothelial growth factor (VEGF) and its receptor in relation to prostate cancer risk. Prostate, 70(4), 341-352. https://doi.org/10.1002/pros.21067

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

In: Prostate, Vol. 70, No. 4, 01.03.2010, p. 341-352.

Research output: Contribution to journalArticle

Vancleave, TT, Moore, JH, Benford, ML, Brock, GN, Kalbfleisch, T, Baumgartner, RN, Lillard, JW, Kittles, RA & Kidd, LCR 2010, 'Interaction among variant vascular endothelial growth factor (VEGF) and its receptor in relation to prostate cancer risk', Prostate, vol. 70, no. 4, pp. 341-352. https://doi.org/10.1002/pros.21067
Vancleave TT, Moore JH, Benford ML, Brock GN, Kalbfleisch T, Baumgartner RN et al. Interaction among variant vascular endothelial growth factor (VEGF) and its receptor in relation to prostate cancer risk. Prostate. 2010 Mar 1;70(4):341-352. https://doi.org/10.1002/pros.21067
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. / Interaction among variant vascular endothelial growth factor (VEGF) and its receptor in relation to prostate cancer risk. In: Prostate. 2010 ; Vol. 70, No. 4. pp. 341-352.
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