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Protein Profiling for the Identification of Serum Biomarkers for Early Detection and Prevention of Breast Cancer in African American Women
Protein profiling for the identification of serum biomarkers for early detection and prevention of breast cancer in African American women.
Background: Breast cancer kills more than 40,000 women in the US every year. It is the most prevalent form of cancer and is the second leading cause of death in women in the U.S. Although breast cancer death rates are currently declining in women, African American (AA) women continue to have a higher death rate from breast cancer than white women. This differential has been attributed partly to earlier onset, late stage at diagnosis, and likelihood of being diagnosed with estrogen-receptor-negative tumors or more aggressive tumors among AA women. Important contributing factors suggested for breast cancer are hormonal, genetic, environmental and socioeconomic. Studies indicate that polymorphisms such as the CYP1A1 Msp1 and UGT1A1 may serve as markers of increased susceptibility to breast cancer in AA women. The identification of markers that will enable early detection of changes in proteins in breast epithelial cells to the pre-tumorigenic phenotype is crucial to the prevention of breast cancer. Initial efforts have already identified many markers of potential clinical interest. Several databases have been generated that include proteomic profiles of human breast cancer biomarkers. Our preliminary studies on 96 DDT-exposed Triana women from Alabama, of which 95% were AA, revealed a breast cancer prevalence of 18% based on 17 cases. Based on these findings we propose to explore genetic susceptibility and environmental impact on breast cancer in AA women by examining the protein profiles of breast cancer patients and healthy women. We propose to conduct a cross-sectional case-control study to identify serum biomarkers. We will enrich the genetic diversity to study genetic susceptibility and environmental exposures by including the DDT-exposed rural Southeast AA women from Alabama with African and black Caribbean American women from the Desert Sierra Region of California. We will utilize proteomics technology to identify biomarkers for early detection of breast cancer. Hypothesis: Pre-cancerous changes taking place within the mammary tissue may be reflected in biomarker patterns. A comparison of the protein profiles of breast cancer patients against those of noncancer controls will allow the identification of potential biomakers that can detect breast cancer at early stages. Xenoestrogens such as DDT that bind to estrogen receptors may enhance the expression of proteins that may increase risk for breast cancer. Specific Aims: (1) To identify biomarkers for early detection of breast cancer by comparing the protein profiles of women diagnosed with breast cancer against healthy controls; (2) To investigate the role of DDT as a risk factor for breast cancer, by comparing DDT exposed and unexposed samples obtained from Triana population in Alabama; and (3) To disseminate educational materials on breast cancer control and prevention to subjects enrolled in the study. Study Design: We will utilize proteomic technology to identify proteomic patterns in serum that distinguish pre-neoplastic from neoplastic disease in breast tissue. A total of 100 serum samples will be analyzed. This would include serum from 30 breast cancer patients, 30 healthy controls, 20 DDT exposed and 20 DDT unexposed subjects. The 40 serum samples from AA Triana women from Alabama were collected and stored from a previous biomarker study on lymphocytes funded by the Department of Defense. The Desert Sierra Cancer Surveillance group will recruit the 60 AA subjects from Desert Sierra Region of California into the study. To detect abnormal changes in the breast tissue we will first separate them on a 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Proteins of interest will then be analyzed with mass spectrometry (MALDI-TOF). The parent polypeptides will be identified by comparing the tryptic peptide masses generated by MS with predicted tryptic peptides from all known polypeptides using the MASCOT data base search engine, accessed at www.matrixscience.com. Confirmation of a protein's identity and/or its modification will be accomplished by sequencing selected tryptic peptides on a Qtof MS. Potential Outcomes and Benefits of the Research: This study will allow the early detection and prevention of breast cancer among AA women. Serum proteomic patterns might ultimately be applied in medical screening as a supplement for diagnostic purposes and evaluation, which will provide better prognosis, especially for at-risk groups such as AA women. Women participating in the study will be educated on prevention and/or control of breast cancer.
Identification of breast cancer markers for early detection and prevention in African American women
Background: Breast cancer kills more than 40,000 women in the US every year. It is the most common cancer and the second leading cause of death in women in the U.S. African American (AA) women have increased incidence of breast cancer deaths compared with white women. The death rate for AA women in the age 20-49 category is 17.39 per hundred thousand, whereas for white women it is 12.26. This increased incidence of death among AA women has been attributed to the occurrence of breast cancer at a younger age, having more advanced-stage breast disease at diagnosis and developing more aggressive tumors. Important contributing factors suggested are hormonal, genetic, environmental and socioeconomic factors. In our previous preliminary study that included 94% AA women, breast cancer was 18% among women who consumed DDT-contaminated fish. Several studies suggest that DDT can mimic estrogens, the group of hormones that increase breast cancer risk. Studies have also shown that certain genes in AA women make them more likely to develop breast cancer. We therefore propose to conduct a study to understand the role of genetic and environmental factors in breast cancer among AA women. We will identify markers of early-stage breast cancer and plan to enrich the diversity of our study population by including AA women from our previous study from Alabama and AA women from the Desert Sierra Region of California. We will utilize proteomics technology. Proteomics is a new field that includes the systematic study of patterns of proteins expressed in living organisms. Proteomics can be used to identify proteins that cause problems and removing or replacing them could help cure or prevent cancer. A comparison of proteins in normal cells or early stage breast cancer, which has a high cure rate with late stage breast cancer with high death rate, will allow identification of potential biomarkers that can detect breast cancer earlier and keep it from progressing. Hypothesis: We expect that changes taking place in the mammary gland prior to the appearance of breast cancer will be reflected in proteins that will appear in the blood. Determining the differences in proteins of early stage breast cancer with healthy controls will allow the identification of potential biomarkers that can predict breast cancer. Environmental factors such as the pesticide DDT that mimic estrogens may affect the levels of these proteins. Specific aims: (1) To identify markers for early detection of breast cancer by comparing proteins in women who are diagnosed with breast cancer against healthy women; (2) To examine if the environmental estrogen DDT affects the levels of potential biomarkers for breast cancer; and (3) To provide educational materials on breast cancer control and prevention to subjects enrolled in the study. Study Design: A total of 100 blood samples will be analyzed. This would include blood from 30 breast cancer patients, 30 healthy controls, as well as 20 DDT-exposed and 20 DDT-unexposed subjects from the Triana population from Alabama. The 40 blood samples from AA Triana women from Alabama were collected and stored from a previous biomarker study on lymphocytes funded by the Department of Defense. The Desert Sierra Cancer Surveillance group will recruit the 60 AA subjects from Desert Sierra Region of California into the study. Potential Outcomes and Benefits of the research: This technology could be used to quickly identify early stage cancer patients by testing the blood and matching it with drugs tailored specifically for the patient. Early detection will help the prevention of the high mortality rates of breast cancer among African American women. Blood protein patterns might ultimately be applied in medical screening for the diagnosis of breast cancer.