||5R03CA096436-02 Interpret this number
||Michigan State University
||Breast Cancer Gene-Diet Interaction Us Polish Migrants
DESCRIPTION (provided by applicant):
Polish women experience a breast cancer (BC) incidence one-third that of US
women, yet recent studies of Polish immigrants to the West show BC mortality
rates for immigrants similar to the rates of the host country. In 1997, the
National Cancer Institute funded a five-year study entitled: "Breast Cancer in
Women of Polish Ancestry," to study the major determinants of this disparity.
We are currently in the process of conducting this study, known in the field
as the Polish Women?s Health Study (PWHS). It consists of two parallel,
population-based case-control studies of 20-79 years old incident BC cases in
two populations: 1) Polish-born immigrants (Cook County and Detroit
Metropolitan Area, US), and 2) Polish-natives (Gliwice, Katowice, Poznan,
Bialystok, Poland). The main dietary hypothesis of the PWHS is that
consumption of cruciferous vegetables, a staple component of the traditional
Polish diet, reduces BC risk.
A major known risk factor for developing BC is a woman?s lifetime exposure to
estrogen (ES). Experimental animal and biochemical studies have shown that
metabolites of cruciferous vegetables, including indole-3-carbinol (I3C),
indolo[3,2-b]carbazole (ICZ) and isothiocyanates, can, in certain situations,
inhibit the carcinogenic effects of ES in in vitro assays and the development
of mammary cancer in experimental animals. To investigate the pathway of
action of cruciferous vegetables in humans, we propose to extend the currently
funded PWHS to examine the role of specific polymorphisms in genes involved in
ES metabolism, as well as the levels of urinary ES metabolites in the
development of BC. Cruciferous vegetable metabolites have the potential to
regulate expression of the genes and their polymorphisms, which, in turn, may
alter ES metabolism in favor of the less estrogenic metabolite (detectable in
urine) and thus decrease BC risk.
To accomplish this goal, we need to collect: 1) "mouthwash" buccal cell
samples to isolate the DNA to analyze for polymorphisms, and 2) 60 ml urine
samples to measure ES metabolites. Thus, the specific aim of this proposal is
to collect and store "mouth-wash" buccal cell samples and 60 ml urine samples
from 300 BC cases and 300 controls already participating in the PWHS in the
US. Scientifically, the PWHS provides us with a unique opportunity to examine
the possible contribution of genetic factors involved in ES metabolism and
their interaction with cruciferous vegetables in a population that has a wide
range of cruciferous vegetable consumption.
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