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Detecting gene-gene interactions in prostate disease in African American men

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BioMed Central
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  • Biology
  • Medicine

Abstract

Detecting gene-gene interactions in prostate disease in African American men PROCEEDINGS Open Access Detecting gene-gene interactions in prostate disease in African American men R Renee Reams1*, Krishna Rani Kalari2, Honghe Wang3, Folakemi T Odedina4,5, Karam FA Soliman1, Clayton Yates3 From The Science of Global Prostate Cancer Disparities in Black Men Jacksonville, FL, USA. 27-29 August 2010 Abstract Background: The most common male malignancy in the United States is prostate cancer; however its rate of occurrence varies significantly among ethnic groups. In a previous cDNA microarray study on CaP tumors from African American (AA) and Caucasian (CA) patients, we identified 97 candidate genes that exhibited opposite gene expression polarity with respect to race groups; genes up-regulated in AA were simultaneously down-regulated in CA. Purpose: The purpose of this study was to narrow the 97 member gene list, to a smaller number of genes in order to focus studies on a limited number of genes/SNPs that might explain prostate cancer disparity in African Americans. Methods: We performed genotype-phenotype, SNP and expression transcript levels correlations using HapMap Yoruba population with 85 of our 97 prostate candidate genes using SCAN database. Results: Findings revealed an association of SNPs surrounding ABCD3 gene with basal gene expression of RanGAP1 is important in prostate tumors in AA. Hence, to confirm our results in clinical biospecimen, we monitored expression of ABCD3 in a novel panel of African American and Caucasian prostate cancer paired cell lines. The LNCaP, C4-2B showed 2-fold increase; MDA-2PC-2B cell line, derived from AA, showed highest fold- change, 10-fold. The EGFR over expressing DU-145 WT cell line exhibited a 4-fold increase in expression relative to non transfected DU-145 prostate cell lines. Furthermore, Ingenuity Network analysis implicated our AA prostate candidate genes are involved in three network hubs, ERK, MapK and NFkB pathways. Conclu

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