Breast Cancer Gene-Diet Interaction US Polish Migrants

乳腺癌基因与饮食的相互作用 美国波兰移民

• 批准号: 6653259
• 负责人: DOROTHY R PATHAK
• 金额: $ 7.48万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653259
• 关键词: Cruciferae; Poland; biomarker; breast neoplasms; clinical research; dietary constituent; estrogens; female; gene environment interaction; genetic polymorphism; genetic susceptibility; human subject; immigrant; lifestyle; neoplasm /cancer epidemiology; nutrition aspect of cancer; nutrition related neoplasm /cancer; nutrition related tag; steroid hormone metabolism

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.

描述(由申请人提供)： 波兰女性患乳腺癌的几率仅为美国的三分之一 女性，然而最近对波兰移民到西方的研究表明公元前死亡 移民的比率与东道国的比率相似。1997年， 美国国家癌症研究所资助了一项为期五年的研究，题为： 波兰血统的妇女，“研究这种差异的主要决定因素。 我们目前正在进行这项研究，这项研究在现场是已知的 作为波兰妇女？S健康研究(PWHS)。它由两个平行的， 湖北省20~79岁儿童乙型肝炎发病人群病例对照研究 两个人口：1)波兰出生的移民(库克县和底特律 美国大都会地区)和2)波兰原住民(Gliwice，Katowice，Poznan， 比亚里斯托克，波兰)。PWHS的主要饮食假设是 消费十字花科蔬菜，这是传统 波兰饮食，降低患BC的风险。 已知的罹患BC的一个主要风险因素是女性？S终身暴露于 雌激素。实验动物和生化研究表明， 十字花科蔬菜的代谢物，包括吲哚-3-甲醇(I3C)， 吲哚[3，2-b]咔唑(ICZ)和异硫氰酸酯，在某些情况下， 抑制ES的体外致癌作用及其研究进展 在实验动物中发现乳腺癌。为了研究……的途径 十字花科蔬菜在人体内的作用，我们建议延长目前的 资助PWHS研究特定多态在参与基因中的作用 ES代谢，以及尿中ES代谢物的水平 公元前的发展。十字花科蔬菜的代谢物有可能 调节基因的表达和它们的多态，进而可能 改变ES代谢，有利于雌激素含量较低的代谢物(可在 尿液)，从而降低患BC的风险。 为了实现这一目标，我们需要收集：1)“漱口水”口腔细胞 用于分离DNA以进行多态分析的样本，以及2)60毫升尿液 用于测量ES代谢物的样本。因此，这项提议的具体目的是 收集和储存口腔细胞样本和60毫升尿样 从300个BC病例和300个对照组已经参加了PWHS在 我们。从科学上讲，PWHS为我们提供了一个独特的机会来研究 遗传因素在ES代谢中的可能作用 它们与十字花科蔬菜的相互作用 十字花科蔬菜的消费范围。