Dietary lignan effects on hormone, growth, and signaling factors in breast tumors

膳食木酚素对乳腺肿瘤激素、生长和信号因子的影响

• 批准号: 7386237
• 负责人: Susan E McCann
• 金额: $ 9.06万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-12 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7386237
• 关键词: Affect; Age; Antioxidants; Apoptosis; Body mass index; Breast; Cancer Etiology; Cancer Prognosis; Caspase; Cell Proliferation; Characteristics; Class; Clinic; Clinical; Data; Databases; Development; Diet; Dietary Component; Dietary Lignans; Dietary intake; Dose; ERBB2 gene; Enrollment; Enzymes; Epidemiologic Studies; Estrogen Receptor Status; Estrogen Receptors; Estrogen receptor negative; Estrogens; Exposure to; Family; Food; Frequencies; Friends; Growth; Growth Factor; Growth and Development function; Histologic; Hormones; Human; IGF1 gene; Insulin-Like Growth Factor I; Intake; Invasive; Investigation; Laboratories; Lignans; Literature; Malignant Neoplasms; Mammary Neoplasms; Measures; Metabolism; Modification; Numbers; Nutrient; Participant; Pathway interactions; Patients; Phenotype; Phytoestrogens; Plants; Plasma; Population; Production; Protein Biosynthesis; Questionnaires; Range; Rate; Reproductive History; Research; Resources; Risk; Risk Factors; Roswell Park Cancer Institute; Sampling; Signal Pathway; Signal Transduction; Somatotropin; Tissues; Tumor Markers; Tumor Subtype; Tumor Tissue; Urine; Woman; Work; burden of illness; cancer risk; cancer type; carcinogenesis; dietary supplements; flaxseed lignan; malignant breast neoplasm; neoplasm resource; outcome forecast; prognostic; protective effect; protein expression; response; soy; steroid hormone; tumor; tumor growth

DESCRIPTION (provided by applicant): Several epidemiologic studies have shown reduced breast cancer risks associated with higher exposure to dietary lignans. Recently, we and others have further shown reduced risks of estrogen receptor (ER) negative breast cancer in women with high versus low dietary intakes, suggesting that the protective effects might be more effective in certain sub-types of cancer. ER status, as well as a number of other tumor characteristics, has been associated with breast cancer prognosis. Although experimental evidence supports the potential for dietary lignans to favorably affect many of these tumor markers, much of the laboratory work has used pharmacologic doses of lignans from flaxseed. Besides the limited data regarding lignan intakes and ER status, an examination of the effect of commonly consumed ranges of dietary lignan intakes on other prognostic and predictive tumor characteristics has not been conducted. Lignans constitute the largest contribution to phytoestrogen intakes among Western populations where soy intake is generally low, and intakes can range widely depending upon which foods are consumed. The wide range of possible intakes is important as experimental evidence suggests that phytoestrogen actions often are concentration dependent, and it is unclear whether amounts consumed via diet produce the same effects as pharmacologic doses available as dietary supplements. Elucidation of the effects of a wide range of phytoestrogen levels is necessary to adequately understand the mechanisms by which lignan intake can affect tumor growth and development. Roswell Park Cancer Institute (RPCI) has developed a core resource for cancer related research. The Data Bank and Biorepository (DBBR) is a comprehensive information and sample bank containing biospecimens and associated clinical and epidemiologic data. The data and biospecimens are donated by RPCI patients who have cancer, or who are at risk for cancer, and their accompanying family and friends. The Breast Clinic at RPCI actively enrolls patients into the DBBR with accruals of approximately 300 women with breast cancer per year. Tumor tissue is available for the majority of the DBBR participants, and a majority also provides extensive epidemiologic data, including a detailed food frequency questionnaire. Within the framework of this unique and rich resource, we propose to conduct an investigation of dietary lignan intakes with a number of tumor characteristics associated with prognosis in breast cancer. Using tissue blocks from 500 women with incident, primary, histologically-confirmed invasive breast cancer enrolled in the DBBR, and measures of dietary lignan intakes from the DBBR food frequency questionnaire, we will evaluate the following specific aims: 1) examine tumor proliferation (Ki-67), apoptosis (caspase), and tumor growth (Ki- 67:caspase ratio) rates associated with lignan intakes; 2) examine growth factor and signaling pathway protein expression (ERa, ER¿, ERa: ER¿ ratio, PgR, HER2, IGF1, IGFIR) associated with dietary lignan intakes; and 3) examine the association of breast tumor subtype (luminal A, luminal B, HER2, and basal-like) with dietary lignan intakes. We will also investigate the potential modification of the associations between dietary lignan intakes and tumor characteristics by characteristics such as age, body mass index, reproductive history, nutrient intakes, and other related data. Lignans are plant compounds that can act as hormones or restrict cancer growth through other mechanisms. The proposed study will investigate the association of dietary lignan intakes, as amounts commonly consumed in usual diets, with several hormone and growth-related tumor characteristics, many of which are related to breast cancer prognosis. The results of this study may provide us with important information that can be useful in understanding the effect of diet on development of different breast cancer sub-types.

描述（由申请人提供）：几项流行病学研究表明，乳腺癌风险降低与膳食木脂素暴露量增加有关。最近，我们和其他人进一步表明，高饮食摄入量与低饮食摄入量的女性患雌激素受体（ER）阴性乳腺癌的风险降低，这表明这种保护作用可能对某些癌症亚型更有效。ER状态以及许多其他肿瘤特征与乳腺癌预后相关。尽管实验证据支持膳食木脂素对许多肿瘤标志物产生有利影响的潜力，但大部分实验室工作都使用了来自亚麻籽的木脂素的药理剂量。除了关于木酚素摄入量和ER状态的有限数据外，还没有进行关于膳食木酚素摄入量的常用消耗范围对其他预后和预测肿瘤特征的影响的检查。木脂素是西方人群中植物雌激素摄入量的最大贡献者，在西方人群中，大豆摄入量通常较低，并且摄入量可以根据所食用的食物而广泛变化。广泛的可能摄入量是重要的，因为实验证据表明，植物雌激素的作用往往是浓度依赖性的，目前还不清楚通过饮食摄入的量是否会产生与作为膳食补充剂的药理剂量相同的效果。阐明广泛的植物雌激素水平的影响是必要的，以充分了解木脂素摄入量可以影响肿瘤生长和发展的机制。罗斯威尔公园癌症研究所（RPCI）开发了癌症相关研究的核心资源。数据库和生物储存库（DBBR）是一个全面的信息和样本库，包含生物标本和相关的临床和流行病学数据。这些数据和生物样本由患有癌症或有癌症风险的RPCI患者及其陪同的家人和朋友捐赠。RPCI的乳腺诊所积极招募患者进入DBBR，每年约有300名乳腺癌妇女。大多数DBBR参与者都有肿瘤组织，大多数人还提供了广泛的流行病学数据，包括详细的食物频率问卷。在这一独特而丰富的资源框架内，我们建议对膳食木脂素摄入量与乳腺癌预后相关的一些肿瘤特征进行调查。使用来自DBBR中登记的500名患有偶发、原发、组织学证实的浸润性乳腺癌的妇女的组织块，以及来自DBBR食物频率问卷的膳食木脂素摄入量的测量，我们将评估以下具体目标：1）检查肿瘤增殖（Ki-67）、凋亡（caspase）和肿瘤生长（Ki-67）。（Ki- 67：半胱天冬酶比率）率与木脂素摄入量相关; 2）检查生长因子和信号通路蛋白表达（ER α、ER、ER α：ER比率、PgR、HER 2、IGF 1、IGFIR）;和3）检查乳腺肿瘤亚型（管腔A、管腔B、HER 2和基底样）与膳食木脂素摄入的关联。我们还将调查饮食木脂素摄入量和肿瘤特征之间的关联的潜在修改，如年龄，体重指数，生育史，营养摄入量和其他相关数据。木脂素是植物化合物，可以作为激素或通过其他机制限制癌症生长。这项拟议的研究将调查膳食木脂素摄入量与几种激素和生长相关肿瘤特征的关系，其中许多与乳腺癌预后有关。这项研究的结果可能为我们提供重要的信息，有助于了解饮食对不同乳腺癌亚型发展的影响。