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    Research Grants Awarded

    Genome Wide Expression Analysis as a Basis for Prognosis in African-American Breast Cancer patients.

    Study Section:
    Population Specific

    Scientific Abstract:
    Background: African American (AA) women <50 yoa have an excess incidence and mortality in breast cancer (BC). We have conducted a pilot study analyzing genome-wide expression differences in self-matched tumor and normal tissue specimens from AA women. Data was compared between familial and sporadic cases and between individual women. Clear genome wide-expression differences were detected between familial and sporadic cases. We extend our studies to a larger cohort of AA patients, as well as Caucasian (Cauc) BC patients. Objective/Hypothesis : Discrete genome expression changes will be identified and shared between AA BC tumor specimens, and these changes will be different from those observed in Cauc samples. Specific Aims : Analyze and compare genome-wide expression profiles in AA and Cauc BC patients. Validate gene expression differences using real-time PCR. Investigate possible chromosome alterations associated with gene expression differences using CHG arrays. Study Design : Fifteen AA and 15 Cauc breast cancer patients will be recruited locally. The protocol and informed consent procedure will be approved by the institutional review board. Study recruitment criteria are: women < 50 years with invasive lymph node positive breast cancer prior to any systemic therapy. Cauc and AA subjects will be matched based on tumor stage, demographic indices, and known risk factors. Tumor and normal tissue samples will be obtained fresh from surgery, total mRNA prepared, labeled with either Cy3 or Cy5 dye, and hybridized to Agilent Whole Human Genome arrays. Data from self-matched tumor and normal breast tissue will be compared within and across ethnic groups. Standard statistical packages developed for microarrays will be used for analyses. Expression differences will be validated using real-time PCR and CHG arrays will be used to analyze possible associated chromosomal abnormalities. Potential Outcomes and Benefits for Research: AA BC patients are noted to have a greater percentage of poorly differentiated BC that occurs at an earlier age and later stage than Cauc women. In this proposal, we will provide a thorough evaluation of whole genome expression differences in BC tissue samples from a small cohort of AA and Cauc BC patients. This unprecedented study may well result in not only further understanding of the biological basis of AA BC , but also insight into genetic etiology of ethnic-specific clinical differences.

    Lay Abstract:
    Background : African American (AA) women <50 yoa have an excess incidence and mortality in breast cancer (BC). Biological reasons have been implicated for this health disparity. To further investigate, we have conducted a pilot study analyzing genome-wide gene expression differences in self-matched tumor and normal tissue specimens from AA women. Data was compared between familial and sporadic cases and between individual women. There are clear gene expression differences between familial and sporadic cases. We extend these first studies to a comparative analysis between AA and Caucasian (Cauc) BC patients. Objective/Hypothesis : Discrete genome expression changes will be identified and shared between AA BC tumor specimens. These changes will be different from those observed in Cauc samples . Specific Aims : Analyze and compare genome-wide gene expression profiles in AA and Cauc BC patients. Validate gene expression differences using a sophisticated technique, real-time PCR. Investigate possible chromosome alterations associated with gene expression differences using state of the art methods. Study Design : Fifteen AA and 15 Cauc breast cancer patients will be recruited locally. The protocol and informed consent procedure will be approved by the institutional review board. Study recruitment criteria are: women < 50 years with invasive lymph node positive breast cancer prior to any systemic therapy. Cauc and AA subjects will be matched based on tumor stage, demographic indices, and known risk factors. Tumor and normal tissue samples will be obtained fresh from surgery, total mRNA prepared, and hybridized to DNA microarrays representing the entire human genome. Data will analyze genes which are differentially expressed in the cancer specimens. Results will be compared within and across ethnic groups. Gene expression differences will be validated using real-time PCR, and state of the art methods will be used to assay for possible chromosomal alterations associated with differential gene expression. Potential Outcomes and Benefits for Research : AA women at all ages have a higher percentage of poorly differentiated BC that occurs at an earlier age and later stage. To investigate these differences, we propose an unprecedented study, which may well result in further understanding of the biological basis of AA BC and insight into the genetic etiology of ethnic-specific clinical differences.