Abstract
Abstract
Disparities in breast cancer stage of presentation and survival rates exist in patients of different ethnicities. These differences are undoubtedly a result of a combination of factors, including socio-economic, lifestyle, tumor characteristics and inherent factors, such as genetic composition. Our group is analyzing the genetic contributions to these disparities, with the goal to increase understanding of the underlying biology, leading ultimately to individualized, ethnic-specific diagnostic and therapeutic approaches. Here we report our results of a recently completed study focusing on gene expression profiling in a multi-ethnic cohort of triple negative breast cancer patients. We analyzed breast cancer and self-matched normal tissue samples from 10 African-American (AA), 10 Hispanic (His), and 10 non-Hispanic white (Caucasian) patients from south Florida. Study samples were cut from FFPE (Formalin Fixed Paraffin-embedded tissue) blocks marked by pathology as normal vs. tumor tissue, and sent to Almac Diagnostics for RNA isolation, cDNA preparation, and hybridization of tumor/normal cDNAs to a breast cancer focused gene expression array (Breast Cancer DSA Research Tool). From the Breast Cancer DSA arrays data, a two-way ANOVA (disease state and ethnicity) was used to identify transcripts with a p-value less than 0.01. Data QC indicated that samples clustered well with respect to ethnicity and adjacent normal vs. tumor tissue. We have identified ethnic-specific expression patterns in the matched normal and tumor samples. Initial pathway analysis using MetaCore Program shows that a number of genes related to the DNA repair pathway are differentially expressed across the ethnicities. In a set of ten DNA repair/cell cycle genes, the direction of change (increased or decreased expression) was the same for all three ethnic groups, however, the level of change differed greatly between ethnic groups. Fold change in this set of ten genes ranged from -6.54 to +5.53 with all being greater than 2 fold change in at least one ethnic group. Additional pathway analysis and validation of these results is ongoing. In follow up to this study, we have initiated parallel analysis in normal tissue samples (reduction mammoplasty) samples from AA and Cau non-cancer patients. Combined analysis of tumor and normal expression data will help to better understand the possible significance of gene expression differences in breast tissue between ethnic groups. These studies have important implications for addressing BC health disparities, as well as tailored approaches to prediction, prevention and treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5602. doi:10.1158/1538-7445.AM2011-5602