Soy Consumption and Breast Tissue Proliferation

大豆消费与乳房组织增殖

• 批准号: 6917401
• 负责人: GERTRAUD MASKARINEC
• 金额: $ 19.72万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-12 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6917401
• 关键词: Japanese American; alternative medicine; breast neoplasms; cancer prevention; caucasian American; cell proliferation; clinical research; developmental nutrition; dietary supplements; estrogen receptors; female; human subject; mammary gland; microarray technology; neoplasm /cancer epidemiology; neoplasm /cancer nutrition therapy; nutrition aspect of cancer; nutrition related tag; nutritional epidemiology; progesterone receptors; proliferating cell nuclear antigen; questionnaires; racial /ethnic difference; soybeans; women' s health

DESCRIPTION (provided by applicant): Within the CAM domain of biologically based therapies, soy and isoflavones play an increasing role. Potential benefits include prevention of cancer, heart disease, and menopausal symptoms. However, a few interventions with soy supplements warned about possible increases in cell proliferation and estrogenic activity in breast tissue. Given the health claims and the growing intake of soy foods and isoflavone supplements among healthy women and breast cancer survivors, it is urgent to investigate the potential adverse effects of soy, especially among survivors. The hypothesis for this project is that women with high soy intake throughout life show lower proliferation in breast tissue than women with low soy intake because they experienced a protective effect from soy since childhood. At the same time, we propose that women with high soy intake in adulthood and low soy intake early in life have greater proliferation in breast tissue than women with high soy intake throughout their life. The study will address the following specific aims: 1. Examine the relation between soy consumption at different times in life and markers of proliferation in normal and cancerous breast tissue among women with Caucasian and Japanese ancestry; 2. Determine whether regular soy intake exerts estrogenic effects on breast cells as assessed by progesterone receptor expression in normal and cancerous breast tissue; and 3. Explore the role of estrogen receptor Beta in the response of normal and cancerous breast tissue to soy intake. This investigation will include Japanese and Caucasian women from a nested case-control study on breast density, a substudy of a multi-ethnic cohort. Cohort members completed a validated food frequency questionnaire. The women in the nested case-control study also reported their lifetime soy history by stage of life. The tissue repository, part of the Hawaii Tumor Registry, has collected discarded pathologic materials, for approximately 85% of all cancer cases diagnosed in Hawaii during 1995 and is in the process of collecting specimens for consecutive years. Potential subjects will be recruited from 400 breast cancer cases diagnosed between 1995 and 1998 and their frequency-matched controls who reported a previous breast biopsy. Based on the 85% statewide coverage and an expected participation rate of 70%, we estimate that we can include neoplastic tissue for 240 breast cancer cases. Furthermore, we anticipate that normal breast tissue will be available in approximately 160 specimens from the women with breast cancer and from approximately 60 control women with previous biopsies. Tissue arrays will be prepared from paraffin-embedded tissue blocks using microarray technology. After histopathologic evaluation, we will perform histomorphometric measurements of the normal breast tissue. On the stained tissue arrays, we will examine two complementary markers of proliferation that work on paraffin blocks and decline little over time, Ki67 and PCNA. In addition, we will assess progesterone receptor expression as a marker of "estrogenic effect" on the breast and estrogen receptors Alpha and Beta as indicators of hormonal responsiveness. Multiple regression models with adjustment for potential confounders will be applied to explore the relation between histopathologic characteristics as the dependent variable with the different measures of soy intake as explanatory variables.

描述（由申请人提供）：在基于生物学的疗法的CAM领域内，大豆和异黄酮发挥了越来越多的作用。潜在的好处包括预防癌症，心脏病和绝经症状。但是，一些与大豆补充剂的干预措施警告说，乳腺组织中可能增加细胞增殖和雌激素活性。鉴于健康妇女和乳腺癌幸存者中大豆食品和异黄酮补充剂的摄入量的日益增长，迫切需要研究大豆的潜在不利影响，尤其是在幸存者中。该项目的假设是，与大豆摄入量低的妇女相比，乳房组织中大豆摄入量高的女性在乳房组织中的增殖较低，因为她们从小就从事大豆的保护作用。同时，我们提出，在成年期和大豆早期摄入量低的大豆摄入量的女性比一生中具有高大豆摄入量的女性的乳房组织增殖更大。该研究将解决以下特定目的：1。检查生活中不同时间和癌性乳腺组织中不同时间的大豆消费与高加索和日本血统的癌性乳腺组织中的增殖之间的关系； 2。确定正常和癌性乳腺组织中孕激素受体表达评估的常规大豆摄入是否会对乳腺细胞产生雌激素作用；和3。探讨雌激素受体β在正常和癌性乳腺组织对大豆摄入的反应中的作用。这项研究将包括来自嵌套的病例对照研究的日本和高加索妇女，该研究是关于乳房密度的，这是多民族同类群体的一种。队列成员完成了经过验证的食品频率问卷。嵌套病例对照研究中的妇女还报告了她们一生的大豆历史。夏威夷肿瘤注册中心的一部分组织存储库已收集了丢弃的病理材料，其中约有85％在1995年夏威夷诊断出的所有癌症病例中，并且连续收集标本。潜在受试者将从1995年至1998年期间诊断的400例乳腺癌病例中招募潜在受试者，并报告了先前的乳房活检的频率匹配对照。根据全州范围85％的覆盖范围和70％的预期参与率，我们估计我们可以在240例乳腺癌病例中加入肿瘤组织。此外，我们预计，来自乳腺癌女性的大约160个标本以及大约60名先前活检的女性的乳房组织将有正常的乳房组织。组织阵列将使用微阵列技术从石蜡包裹的组织块中制备。在组织病理学评估后，我们将对正常乳腺组织进行组织形态测量。在染色的组织阵列上，我们将检查两个在石蜡块上起作用的增殖的互补标记，并且随着时间的流逝，Ki67和PC​​NA几乎没有下降。此外，我们将评估孕酮受体表达，作为对乳腺癌和雌激素受体α和β的标志，作为激素反应性的指标。对潜在混杂因素进行调整的多元回归模型将应用于探索组织病理特征作为因变量与大豆摄入量的不同度量作为解释变量的关系。