Current research focus and ongoing cancer
|A) What is the role of DNA
repair as a risk factor for breast and skin cancer?
B) What is the role of DNA repair genes and BRCT proteins as
potential therapeutic targets
in cancer? (collaboration with Dr. Alvaro Monteiro,
Moffitt Cancer Center)
C) DNA microarray analysis of key DNA repair genes
associated with a significant change
in risk of developing in breast and skin cancer.
D) Identify epidemiological and epigenetic factors
associated with changes in DNA repair
capacity in humans (collaboration with Dr. Rafael Guerrero
and Dr. David Sidransky,
Johns Hopkins School of Medicine).
E) Identification of HPV serotypes associated with
non-melanoma skin cancer.
As part of an ongoing large scale population study funded
by the Minority Biomedical Research Support (MBRS) Support
of Competitive R esearch (SCORE) Program and the National
Institute of General Medical Sciences (NIGMS), we are
currently pursuing the following Specific Aims in breast
Aim 1. Compare the DNA repair capacity (DRC) in women
with and without breast carcinoma in Puerto Rico using a
host cell reactivation assay that provides a direct
measurement. It is hypothesized that participants with
breast carcinoma have a lower age-adjusted DRC than women
without breast carcinoma.
Aim 2. Obtain epidemiological data from participants
in order to determine risk factors for breast carcinoma.
Each participant (controls and cases) will be administered
an epidemiological questionnaire soliciting information on
variables that can provide an estimate of breast carcinoma
risk in relation to familial, genetic, hormonal and
environmental factors. Statistical correlations between the
various study variables and risk of developing breast
carcinoma will provide valuable information for the
development of effective strategies for cancer prevention
and control for future studies.
Aim 3. Compare whether the levels of expression of
DNA repair genes is correlated with the DNA repair capacity
of women with breast carcinoma. It is hypothesized that
women with BC have an altered expression of key DNA repair
genes. The expression of DNA repair genes in BC tumors will
be analyzed in women with low, normal, and high DRC.
Microarray analysis will be utilized to identify potential
DNA repair genes associated with the risk of breast
carcinoma and to test whether candidate DNA repair genes can
be utilized to predict DNA repair capacity of women with
Aim 4. Examine whether tumor grade and size and
presence of axillary lymph node metastasis are associated
with the level of DNA repair capacity and levels of
expression of DNA repair genes. The pathology report will be
analyzed for the presence of axillary lymph node metastasis,
the size of the tumor, the histological grade, and type and
sub-type of breast carcinoma. It is hypothesized that BC
cases with a lower DRC have a higher tumor grade, larger
size, and positive axillary lymph node metastasis when
compared with BC cases with higher DRC. It is also
hypothesized that BC cases with a significant alteration in
the expression of DNA repair genes have a higher tumor
grade, larger size, and positive axillary lymph node
metastasis than BC cases with a normal expression of DNA