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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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