DIETARY FAT, EICOSANOIDS, AND BREAST CANCER RISK

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 性激素介导的癌症，如乳腺癌，在美国是一个严重的问题。 重要的是要为这些疾病制定安全有效的预防策略。 流行病学证据和动物研究表明，膳食脂肪与性激素介导的癌症的发展风险有关。 特别是，高摄入的omega-6脂肪酸会增加风险，而omega-3脂肪酸与风险降低有关。 虽然膳食脂肪和性激素介导的癌症之间的关联尚不清楚，但可能是由于内分泌平衡，类花生酸产生或免疫功能的机制。 这一建议解决了饮食中总脂肪和脂肪酸对绝经后妇女性激素浓度影响的重要问题。 具体目标是：1）评价总脂肪和ω-3脂肪酸摄入对绝经后妇女的血浆和尿性激素水平的影响，2）评价脂肪酸的血浆浓度与血浆和尿性激素的血浆浓度之间的关系，和3）评价总脂肪和ω-3种脂肪酸对性激素浓度与尿前列腺素E2和血栓素B2浓度之间的关系。 为了评估这些关系，我们将进行一项控制良好的喂养研究，以评估膳食脂肪和脂肪酸的影响。 在8周喂养期内测试的饮食包括“高风险”美国饮食（40%脂肪）、低脂肪饮食（20%脂肪）和补充ω-3脂肪酸的低脂肪饮食（23%脂肪）。将在基线以及每种饮食治疗的第4周和第8周进行尿和血浆性激素、血浆脂肪酸和尿类花生酸、前列腺素E2和血栓素B2的终点测量。

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. Sex hormone mediated cancers, such as breast, present a significant problem in the United States. It is important to develop safe and effective preventative strategies for these diseases. Epidemiological evidence and animal studies show that dietary fat is associated with risk of development of sex hormone mediated cancer. Specifically, that a high intake of omega-6 fatty acids increases risk while omega-3 fatty acids are associated with risk reduction. Although the associations between dietary fat and sex hormone mediated cancers is unclear, it is likely due to mechanisms of endocrine balance, eicosanoid production, or immune function. This proposal addresses important questions about the effects of dietary total fat and fatty acids on sex hormone concentrations in postmenopausal women. The specific objectives are: 1) to evaluate the effects of total fat and omega-3 fatty acid intake on plasma and urinary sex hormone levels in postmenopausal women, 2) to evaluate the relationship between plasma concentrations of fatty acids and of plasma and urinary sex hormones, and 3) to evaluate the effects of total fat and omega-3 fatty acids on the association between sex hormone concentrations and urinary prostaglandin E2 and thromboxane B2 concentrations. In order to evaluate these relationships we wil conduct a well-controlled feeding study to evaluate dietary fat and fatty acid effects. The diets to be tested in 8 week feeding periods include a "high risk" American diet (40% fat), a low fat diet (20% fat) and a low fat diet with supplemental omega-3 fatty acids (23% fat). Endpoint measures of urinary and plasma sex hormones, plasma fatty acids, and the urinary eicosanoids, prostaglandin E2 and thromboxane B2, will be made at baseline, and at 4 and 8 week of each dietary treatment.