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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Research Articles

Genes Associated with Prostate Cancer Are Differentially Expressed in African American and European American Men

Isaac J. Powell, Greg Dyson, Susan Land, Julie Ruterbusch, Cathryn H. Bock, Steve Lenk, Mehsati Herawi, Richard Everson, Craig N. Giroux, Ann G. Schwartz and Aliccia Bollig-Fischer
Isaac J. Powell
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Greg Dyson
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Susan Land
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Julie Ruterbusch
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Cathryn H. Bock
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Steve Lenk
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Mehsati Herawi
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Richard Everson
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Craig N. Giroux
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Ann G. Schwartz
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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Aliccia Bollig-Fischer
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
1Barbara Ann Karmanos Cancer Institute; 2Wayne State University Department of Urology, 3Wayne State University Department of Oncology, 4Wayne State University School of Medicine, 5Wayne State University Department of Pathology, Detroit, Michigan; and 6Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, Farmington, Connecticut
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DOI: 10.1158/1055-9965.EPI-12-1238 Published May 2013
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  • Figure 1.
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    Figure 1.

    Functional Interaction Network from analysis of genes upregulated in prostate tumors from AAM or EAM. The network derived from Ingenuity Pathways analysis shows a high degree of inherent, functional interrelatedness for a subset of factors from the analyzed gene expression datasets (AAM blue, EAM yellow). Results suggest that AAM and EAM prostate tumors are distinguished at gene level with NFKB and inflammatory cytokine factors primarily upregulated in PCa from AAM; EAM-upregulated genes are centered on TNF. Edges (lines) linking members of both sets to P38MAPK, TNF, and PI3K/AKT genes suggests that the associated pathways are operating to some extent in both EAM and AAM contexts.

  • Figure 2.
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    Figure 2.

    Boxplots of the log base 2 expression levels for genes mapped to the functional interaction network. The genes identified in the functional interaction network in Fig. 1 were stratified by race and the individual genes measured by the DASL assay identified as the PI3K complex genes are named. The stars at the bottom of the graph indicate statistically significant differences between races. As TNF is a central hub in the network, it is included in the graph even though it is not statistically significant.

  • Figure 3.
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    Figure 3.

    Plot of the first 2 principal components, computed from all 517 genes on 639 tumor samples (270 AAM, 369 EAM) and 165 control samples (82 AAM, 83 EAM). Although all of the control samples had a matching tumor sample and thus are expected to be highly correlated with the respective tumor sample, the samples clustered by tumor/control status, regardless of race. This implies that the expression profile of the tumor samples is similar across races and different than the profile of the control samples, which are also similar across races.

Tables

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  • Table 1.

    Descriptive statistics of the samples under study

    VariableAAM (n = 270)EAM (n = 369)P-value
    Age62.76 (6.35)61.74 (6.82)0.054
    VariableLevelsAAM (n = 270)EAM (n = 369)P-value
    Gleason's grade0.177
    ≤692 (0.34)139 (0.38)
    7 (3 + 4)77 (0.29)122 (0.33)
    7 (4 + 3)60 (0.22)61 (0.17)
    ≥841 (0.15)47 (0.13)
    Gleason's grade categorized0.030
    Nonaggressive169 (0.63)261 (0.71)
    Aggressive101 (0.37)108 (0.29)

    NOTE: Age is described as mean and SD, whereas the Gleason's grade variables are presented as number of observations and percentage. The P-values in the table are a result of a test of the difference between races using a t-test for age and a χ2 test for the Gleason's grade variables.

    • Table 2.

      Mean expression ratio of EAM as compared to AAM for the functionally linked genes from the network in Fig. 1

      GeneMean EAM relative to AAM expressionP-value
      ADIPOQ1.120.002
      AKT10.940.026
      ALOX121.090.003
      ALOX151.24<0.001
      ALOX15B0.880.022
      BMP20.910.030
      CGA1.120.001
      CXCR40.87<0.001
      CYP19A11.060.029
      ERG1.62<0.001
      FASN0.900.009
      IL1B0.890.001
      IL60.78<0.001
      IL80.84<0.001
      NFKB10.960.048
      PIK3C31.050.033
      PIK3CA1.080.004
      PIK3R11.070.018
      PLA2G2A1.16<0.001
      TGFB10.91<0.001
      TIMP31.070.017
      TNF0.970.445

      NOTE: The t test P-value testing the difference in expression between races is included in the table. Individual genes measured on the assay that were associated with the PI3K complex are named in the table.

      Additional Files

      • Figures
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      • Supplementary Data

        Files in this Data Supplement:

        • Supplementary Tables 1 - 2, Figure 1 - PDF file - 114K, Suppl Table 1 - List of the 517 genes whose expression was measured by DASL microarray analysis of RNA from FFPE specimens. Supplemental Table 2. Mean difference and t-test p-value between the computed DDCt from EAM minus the computed DDCt from AAM from the validation sample of 16 AAM and 16 EAM. Supplemental Figure 1. Plot of the first 2 principal components, computed from all 517 genes on 163 patient tumor samples (80 AAM, 83 EAM) with the corresponding matched normal samples.
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      Cancer Epidemiology Biomarkers & Prevention: 22 (5)
      May 2013
      Volume 22, Issue 5
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      Genes Associated with Prostate Cancer Are Differentially Expressed in African American and European American Men
      Isaac J. Powell, Greg Dyson, Susan Land, Julie Ruterbusch, Cathryn H. Bock, Steve Lenk, Mehsati Herawi, Richard Everson, Craig N. Giroux, Ann G. Schwartz and Aliccia Bollig-Fischer
      Cancer Epidemiol Biomarkers Prev May 1 2013 (22) (5) 891-897; DOI: 10.1158/1055-9965.EPI-12-1238

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      Genes Associated with Prostate Cancer Are Differentially Expressed in African American and European American Men
      Isaac J. Powell, Greg Dyson, Susan Land, Julie Ruterbusch, Cathryn H. Bock, Steve Lenk, Mehsati Herawi, Richard Everson, Craig N. Giroux, Ann G. Schwartz and Aliccia Bollig-Fischer
      Cancer Epidemiol Biomarkers Prev May 1 2013 (22) (5) 891-897; DOI: 10.1158/1055-9965.EPI-12-1238
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