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

基本信息

批准号：
6492908
负责人：
DOROTHY R PATHAK
金额：
$ 7.45万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-01 至 2004-08-31
项目状态：
已结题

项目摘要

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）：波兰女性乳腺癌 (BC) 发病率是美国女性的三分之一女性，但最近对西方波兰移民的研究表明不列颠哥伦比亚省的死亡率移民的税率与东道国的税率相似。 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“乳腺癌在波兰血统的女性”，研究这种差异的主要决定因素。我们目前正在进行这项业内已知的研究如波兰妇女健康研究 (PWHS)。它由两个平行的、对 20-79 岁 BC 病例进行的基于人群的病例对照研究两种人群：1）波兰出生的移民（库克县和底特律美国大都市区）和 2）波兰本地人（格利维采、卡托维兹、波兹南、波兰比亚韦斯托克）。 PWHS 的主要饮食假设是消费十字花科蔬菜，这是传统饮食的主要组成部分波兰饮食，降低乳腺癌风险。罹患 BC 的一个已知的主要风险因素是女性一生中接触雌激素（ES）。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)、吲哚并[3,2-b]咔唑（ICZ）和异硫氰酸酯，在某些情况下，可以体外试验和开发中抑制ES的致癌作用实验动物中的乳腺癌。为探究途径十字花科蔬菜对人类的作用，我们建议延长目前的资助 PWHS 来检查相关基因中特定多态性的作用 ES 代谢，以及尿中 ES 代谢物的水平 BC 省的发展。十字花科植物代谢物有潜力调节基因的表达及其多态性，这反过来又可能改变 ES 代谢，有利于雌激素较少的代谢物（可在尿），从而降低 BC 风险。为了实现这个目标，我们需要收集：1）“漱口”颊细胞分离 DNA 进行多态性分析的样本，以及 2) 60 ml 尿液用于测量 ES 代谢物的样品。因此，该提案的具体目标是收集并储存“漱口”口腔细胞样本和 60 毫升尿液样本来自已参与 PWHS 的 300 例 BC 病例和 300 例对照我们。从科学角度来说，PWHS 为我们提供了一个独特的机会来检验 ES代谢中涉及的遗传因素的可能贡献以及它们与具有广泛种群的十字花科蔬菜的相互作用十字花科蔬菜的消费范围。