Breast Cancer Gene-Diet Interaction US Polish Migrants

描述（由申请人提供）： 波兰女性乳腺癌（BC）发病率是美国的三分之一 然而，最近对波兰移民到西方的研究表明， 移民的税率与东道国的税率相似。1997年 国家癌症研究所资助了一项为期五年的研究，题为：“乳腺癌在 波兰经济界的妇女”，以研究这种差距的主要决定因素。 我们目前正在进行这项研究的过程中，已知在该领域 波兰妇女？的健康研究（PWHS）。它由两个平行的， 在20-79岁的BC病例中进行的基于人群的病例对照研究， 两个人口：1）波兰出生的移民（库克县和底特律 大都会区，美国），和2）波兰本地人（格利维采，卡托维兹，波兹南， 比亚韦斯托克，波兰）。PWHS的主要饮食假设是， 十字花科蔬菜的消费，传统的主要组成部分 波兰饮食，降低BC风险。 发展BC的一个主要已知风险因素是女性？的终身暴露 雌激素（ES）。实验动物和生物化学研究表明， 十字花科蔬菜的代谢物，包括吲哚-3-甲醇（I3 C）， 吲哚并[3，2-B]咔唑（ICZ）和异硫氰酸酯，在某些情况下， 在体外试验中抑制ES的致癌作用， 乳腺癌的实验动物。为了研究 十字花科蔬菜在人类中的作用，我们建议扩大目前的 资助PWHS研究特定多态性在参与基因中的作用， ES代谢，以及尿中ES代谢产物的水平， BC的发展。十字花科蔬菜代谢物具有潜在的 调节基因的表达及其多态性，反过来， 改变ES代谢，有利于雌激素性较低的代谢物（在 尿），从而降低BC风险。 为了实现这一目标，我们需要收集：1）“漱口水”颊细胞 样品以分离DNA以分析多态性，和2）60 ml尿液 样品以测量ES代谢物。因此，这项建议的具体目的是 收集并储存“漱口水”口腔细胞样本和60 ml尿液样本 从300例BC病例和300例对照中， 我们从科学的角度来看，PWHS为我们提供了一个独特的机会， 参与ES代谢的遗传因素的可能贡献， 他们与十字花科蔬菜的相互作用在一个人口，有广泛的 十字花科蔬菜的消费范围。

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.