Gene Expression Alterations in Breast Carcinomas from Patients with Racial Differences

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 292-325-Breast & Prostate Cancer
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-303
Adrienne M Bushau*, Sarah A Andres and James L Wittliff
University of Louisville, Louisville, KY
African American women often exhibit more aggressive breast cancers and have a higher mortality rate than Caucasian women. Socioeconomic variances in racial groups do not explain many of the differences observed in clinical behavior of breast carcinomas.  Our goal is to determine dissimilarities in gene expression of breast carcinoma biopsies of white and black patients and to evaluate their relationship to cancer behavior. Using an IRB-approved biorepository and database, gene expression levels were compared in biopsies from white and black patients utilizing microarray analyses of LCM-procured carcinoma cells.  Frozen tissue sections of primary breast carcinomas from de-identified patients were utilized for qPCR analyses.  Total RNA was extracted with the RNeasy Mini Kit (Qiagen), evaluated with the Bioanalyzer (Agilent) and reverse transcribed using iScript (Biorad). QPCR was performed using Power Sybr Green (Applied Biosystems) and relative expression was calculated using Universal Human Reference RNA (Stratagene) as the calibrator and ACTB for normalization. Examination of microarray results of candidate genes revealed that expression levels of CARD11, TRAPPC2L, CRYBB2P1 and PDHA1 were significantly different in carcinomas of African American patients compared to those of Caucasian patients.  Of these genes, PDHA1 expression was correlated with overall survival (P=0.05) when the entire population of 245 breast carcinoma patients was stratified by median expression level without regard to race. Furthermore, PDHA1 expression assessed by microarray was correlated with overall survival of white patients (P=0.04) when stratified by race and gene expression level.  Using qPCR of RNA from intact tissue sections, expression levels of PDHA1, CRYBB2 and TRAPPC2L were analyzed for correlation with survival outcomes. When the entire patient population was stratified by median gene expression level, PDHA1, CRYBB2 and TRAPPC2L were not statistically significant for associations with disease-free or overall survival. However, when stratified by race and median gene expression, increased expression of TRAPPC2L was correlated with longer disease-free survival (P=0.002, HR=8.84) in black patients. These preliminary results support a need for identifying biomarkers to personalize clinical management of breast cancer patients with different racial backgrounds.

Nothing to Disclose: AMB, SAA, JLW

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Sources of Research Support: Supported in by a grant from the R25 NCI Summer Research Program, PHS Grant # 1 R25 CA 134283-1 to AMB.