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 800 BC cases and 800 controls already participating in the PWHS in Poland. 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.
