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Dr. Jaime L. Matta
Title: DNA Repair and Gene Expression Associated with Susceptibility to Breast Carcinoma



Cancer is the second leading cause of mortality in USA and Puerto Rico (PR). Breast carcinoma (BC) is one of the most common types of human cancer in women in the USA and in PR. In Puerto Rican women, BC represented approximately 32% of the cases diagnosed in the year 2000. Changes in the expression of certain genes can modify the risk of BC. The DNA repair capacity (DRC) of the body is a critical system aimed at protecting the integrity and stability of the genome. The focus of this study is to examine the relationship between DNA repair, changes in the expression of DNA repair genes and key pathological and epidemiological characteristics in terms of how these factors affect the risk of breast carcinoma in Puerto Rican women. It is hypothesized that a low DRC is a risk factor for BC in women and is associated with alterations in gene expression and larger, more aggressive and undifferentiated BC tumors. This overall aim will be achieved by pursuing the following specific aims: 1) To determine the DRC in lymphocytes of women with and without breast carcinoma. Preliminary data (Ramos et al. 2004) have shown that women (n=40) in PR with BC have a statistically significant reduction of 36% in age-adjusted DRC compared to controls; 2) Obtain epidemiological data from participants in order to determine familial, genetic, hormonal and environmental factors that influence risk of BC, 3) To determine the level of expression of DNA repair genes in BC tumor samples in participants with low, average and high DNA repair in order to identify potential genes associated with risk of BC; 4) Examine whether tumor grade, size and presence of axillary lymph node metastasis are associated with the level of DRC and levels of expression of DNA repair genes. The host cell reactivation assay will be utilized to measure DRC in blood lymphocytes. Data from a clinical, case-control retrospective study will be stratified by DNA repair capacity and adjusted for age and other factors, if necessary, in order to calculate odds ratios for key BC risk factors. Levels of gene expression in tumor samples will be determined by DNA microarray analysis utilizing the core facilities at H. Lee Moffitt Cancer Center. This is the first large-scale population study utilizing an innovative approach aimed at correlating how DRC, changes and expression of DNA repair genes and key pathological and epidemiological characteristics of BC influence the risk of this disease. By studying the DRC and the expression of DNA repair genes, we may better understand the pathogenesis of breast carcinoma and to identify women at high risk by using combined genetic and environmental risk factors (breast cancer prevention). Identification of specific DNA repair genes associated with BC risk may serve in predicting the prognosis and therapeutic outcome of women with breast carcinoma. This may provide a rationale for developing future patient-based optimal selection of chemotherapeutic agents and radiotherapy protocols.
 


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