EFFECTS OF SOY ISOFLAVONES ON THE PROSTATE, BREAST, AND BONE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。背景：大豆食品富含异黄酮，这是一种“植物雌激素”，虽然非甾体，但具有一些类似雌激素的特性。最近，关于大豆潜在益处的广泛报道导致其在美国的消费量增加，据称其益处包括对前列腺癌、乳腺癌和骨质疏松症的保护作用。有益的证据主要来自流行病学关联和动物或细胞模型的实验室研究。很少有人体临床试验。目的：探讨大豆异黄酮摄入对体外代癌指标、骨密度指标及男女生活质量指标的影响。广义假设：摄入异黄酮对癌症和骨密度指标有积极影响。设计：随机、双盲、交叉试验设计将在三个人群中使用：i)接受雄激素消融治疗的前列腺癌患者；ii)接受激素替代疗法（HRT）的绝经后妇女；iii)未接受激素替代疗法的绝经后妇女。参与者将分别服用异黄酮补充剂和安慰剂，为期2个月。结果将是癌症和骨密度的标志。方法：本项目将重点研究异黄酮作用的基础科学。参与者的血清和血清提取物将与培养的人类细胞系（前列腺癌、乳腺癌和成骨细胞）孵育，并研究雌激素和非雌激素的作用机制。人类血清数据将通过直接将结晶异黄酮（染料木素、大豆苷元和马酚）添加到相同培养的人类细胞系的平行研究来补充。参与者的血清和尿液也将测试骨吸收和形成的标志物。生活质量问题将通过问卷进行评估。启示：尽管许多关于膳食豆制品及其异黄酮的健康声明，大多数都没有经过充分的人体测试。在某些情况下，可能会有副作用。这个为期5年的研究项目旨在建立异黄酮作用的基本机制和途径，这些作用是它们对前列腺、乳房和骨骼的影响的基础。研究结果将与美国大部分患有前列腺癌、乳腺癌和骨质疏松症或有发展风险的人群相关，并可能为大豆和/或一种或多种异黄酮成分的更明确的临床试验提供基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Soy foods are high in Isoflavones, one group of "phytoestrogens", which, although non-steroidal, have some estrogen-like properties. Widespread reports of soy's potential benefits have recently led to its increased consumption in the U.S. Purported benefits include protective effects for prostate cancer, breast cancer, and osteoporosis. Evidence for benefit is derived largely from epidemiological associations and laboratory studies with animal or cell models. There are very few human clinical trials. Objective: To study the effects of soy Isoflavone intake on in vitro surrogate cancer markers as well as bone density markers and quality of life parameters in men and women. Broad hypothesis: Isoflavone intake will favorably effect cancer and bone density markers. Design: A randomized, double-blind, cross-over trial design will be used with three populations: i) men with prostate cancer on androgen ablation therapy; ii) postmenopausal women on hormone replacement therapy (HRT); and iii) postmenopausal women not on HRT. Participants will receive an Isoflavone supplement and placebo each for 2-months. Outcomes will be markers of cancers and bone density. Methods: The project's focus will be on the basic science of Isoflavone action. Participants' serum and serum extracts will be incubated with cultured human cell lines (prostate cancer, breast cancer, and osteoblasts) and estrogenic and non-estrogenic mechanisms of action investigated. The human sera data will be complemented by parallel studies of direct addition of crystalline isoflavones (genistein, daidzein, and equol) to the same cultured human cell lines. Participant's serum and urine also will be tested for markers of bone resorption and formation. Quality of life issues will be assessed with questionnaires. Implications: Although many health claims have been made for dietary soy products and their isoflavones, most have not undergone adequate human testing. Under certain conditions, there may be adverse effects. This 5-yr research program seeks to establish the basic mechanisms and pathways of isoflavone actions that underlie their effects on the prostate, the breast and on bone. Results will be relevant to the large segment of the US population suffering from, or at risk of developing, prostate cancer, breast cancer, and osteoporosis and may provide the basis for more definitive clinical trials of soy and/or one or more of its Isoflavone components.