DIETARY FAT, EICOSANOIDS, AND BREAST CANCER RISK

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。性激素介导的癌症，如乳腺癌，在美国是一个严重的问题。为这些疾病制定安全有效的预防战略十分重要。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生风险有关。具体来说，大量摄入omega-6脂肪酸会增加风险而omega-3脂肪酸会降低风险。虽然膳食脂肪与性激素介导的癌症之间的关系尚不清楚，但这可能是由于内分泌平衡、类二十烷产生或免疫功能的机制。这一建议解决了关于膳食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。具体目的是：1)评价总脂肪和ω -3脂肪酸摄入对绝经后妇女血浆和尿性激素水平的影响；2)评价血浆脂肪酸浓度与血浆和尿性激素的关系；3)评价总脂肪和ω -3脂肪酸对性激素浓度与尿前列腺素E2和血栓素B2浓度之间的关系的影响。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周的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）和添加omega-3脂肪酸的低脂肪饮食（23%脂肪）。终点测量尿和血浆性激素、血浆脂肪酸以及尿二十烷类，前列腺素E2和血栓素B2，将在基线、每种饮食治疗的第4周和第8周进行。

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.