Genetic Research May Advance Understanding of Ethnic Differences in Breast Cancer
Embargo expired: 28-Oct-2012 10:00 AM EDT
Source Newsroom: American Association for Cancer Research (AACR)
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Newswise — SAN DIEGO — For the first time, researchers have provided a direct comparison of gene expression profiles from African-American and East African breast tissue samples, according to results presented at the Fifth AACR Conference on The Science of Cancer Health Disparities, held here Oct. 27-30, 2012.
The research, which began at the University of Miami in Florida and continues at the Translational Genomics Research Institute (TGen), should expand researchers’ understanding of breast cancer across different ethnicities. This knowledge may lead to new preventive, predictive and treatment measures, according to Lisa Baumbach-Reardon, Ph.D., associate professor in TGen’s Integrated Cancer Genomics Division in Arizona and director of TGen’s DNA Diagnostic Laboratory in Cancer Genomics.
Epidemiologic evidence indicates that breast cancer is the second-leading cause of cancer death among African-American women. Compared with Caucasians, African-Americans have a 20 percent higher mortality rate.
“Ethnic-specific differences exist in genes expressed in breast cancer tissue across ethnicities,” said Baumbach-Reardon. “Understanding significant ethnicity-specific differences will help us to better understand how and why breast cancer differs across different ethnicities and will ultimately help us to translate this knowledge into clinical practice.”
Researchers analyzed archived breast cancer pathology samples obtained from either the University of Miami or the Nairobi Cancer Registry. Forty-seven breast cancer samples came from Kenya. After reanalysis, the researchers confirmed that 29 of the Kenyan cases were triple-negative breast cancer; a high percentage of these cases were in an advanced stage and were high-grade.
“It is known that in this African region, breast cancer presents as an advanced-stage disease, composed mainly of poorly differentiated cancers that are less likely to be hormone-responsive (i.e., triple-negative breast cancer),” said Baumbach-Reardon. “This is very similar to the presentation of African-American women with breast cancer in the United States.”
Initial data analyses indicated there are gene expression differences within several key pathways, including signal transduction in the AKT signaling pathway, according to Baumbach-Reardon.
She and her colleagues also presented data on chromosomal aberrations and variants in a subset of the Kenyan samples.
The researchers do not yet fully understand why triple-negative breast cancer is overrepresented in women of African descent, although it is clear that multiple factors play a role, according to Baumbach-Reardon.
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Investigation of Transcriptome Differences in Breast Cancer Tissues from African-American and East African Patients with Triple Negative Breast Cancer. Lisa Baumbach1, Mark Pegram2, Carmen Gomez3, Biju Issac3, Jennifer Clarke3, Merce Jorda3, Mary Ellen Ahearn1, John Carpten1, Peter Bird4. 1TGen, Phoenix, AZ, 2Stanford University, Palo Alto, CA, 3University of Miami Medical School, Miami, FL, 4AIC Kijabe Hospital, Kijabe, Kenya.
INTRODUCTION: Strong epidemiological data supports breast cancer (BC) as the second leading cause of cancer death among African-American (AA) women, with a 20% greater mortality rate than that in Caucasians (Cauc). Collection of similar BC incidence and mortality data for Eastern Africa is limited, with the Nairobi Cancer Registry serving as the primary data collection source. However, it is known that in this African region, BC presents as an advanced-stage disease, comprised mainly of poorly differentiated cancers that are less likely to be hormone responsive.
OBJECTIVES: Our combined investigative team is studying a cohort of indigenous Kenyan breast cancer patients, in order to begin to understand biological similarities and differences between BC in native African and US African patients. Recent gene expression studies conducted by our group suggest differential expression patterns in Triple Negative Breast Cancer (TNBC) across a stage-matched multi-ethnic US cohort. We are extending this focus to similar studies involving native African samples.
METHODS: Archived BC pathology samples (FFPE) were either obtained from University of Miami (C. Gomez; M. Jorda) or from a native African tumor bank (P. A. Bird, Kijabe). Forty-seven BC samples were contributed from Kenya, and re-analyzed (in Miami) for ER/PR/ Her2Neu status, resulting in confirmation of 29 Kenyan TNBC cases. As expected, a high percentage of the Kenyan tumors were advanced stage and high grade. These Kenyan TNBC cases, as well as US AA TNBC cases from Miami, were analyzed by gene expression studies. 10 um sections were cut from each tumor FFPE block, and following RNA isolation and cDNA preparation, hybridized to the Almac breast-enriched gene expression array (Breast Cancer DSA Research Tool). After quality control assessment of array data, unpaired student’s T-test was performed between Kenyan and AA samples, and resulting p-values were corrected for Multiple Testing using Benjamin-Hochberg.
RESULTS: Three sets of differentially expressed genes/probes were extracted using different thresholds: Stringent (P-value ≤ 0.01 & Fold Change ≥ 2.0; 1013 probes); Less Stringent (P-value ≤ 0.02 & Fold Change ≥ 2.0; 1669 probes) ; and Most Significant (P-value ≤ 0.001 & Fold Change ≥ 1.5,136 probes), the latter of which generated hierarchical clustering of the most significant differentially expressed genes. These probe/gene lists were further analyzed using GeneGo pathway analysis. Initial analyses point to possible gene expression differences within several key pathways, including signal transduction in the AKT signalling pathway. Further data set analyses are being performed, including consideration of additional tumor characteristics. The latest data interpretations will be presented.
CONCLUSIONS: This study represents the first direct comparison of gene expression in TNBC specimens across US AA and Kenyan East Africans. These results will be compared with data from our previous ethnic cohort studies. We will strive to correlate all experimental data with available clinical data, and determine possible correlations between genomic signatures, clinical tumor characteristics, and demographic information among and across ethnic groups. Ultimately, this work will contribute to our further biologic understanding of BC across different ethnicities, and thus, development of new preventive, predictive and therapeutic measures.