DIETARY FATTY ACIDS--ROLE IN HORMONALLY MEDIATED CANCER

描述：（申请人描述）导致 性类固醇依赖性癌症的发展，如乳腺癌， 癌症，还没有完全了解，但水平和类型的膳食脂肪消耗 被认为是导致这种癌症的原因。 植物性食物摄入一直与较低的风险有关， 乳腺癌 特定的非营养植物化学物质，如大豆 雌激素，在结构上与性类固醇激素相似， 因此在体内起作用以改变激素代谢和随后的癌症 风险 因为大多数乳腺癌病例似乎涉及一个 强烈的荷尔蒙成分，很可能是膳食脂肪和 植物化学物质可能会影响这种风险。 本申请的总体目标是探索 不同类型的膳食脂肪（因此， 饮食），但不是总脂肪量，对循环类固醇激素 （特别是内源性雌激素）在绝经前妇女。 因此，在喂养 研究1（年），两种饮食，两者都将提供36%的能量， 脂肪和15克膳食纤维（类似于美国饮食），将使用。 的 高饱和脂肪饮食将提供23%的能量作为饱和脂肪。 本申请的具体目的是确定血清是否 性激素和结合蛋白的浓度和尿排泄 受脂肪类型的影响，当脂肪摄入量高，膳食纤维 温和的。 该项目的另一个目标是检查饮食是否 大豆可以缓和饮食中饱和脂肪酸对激素的影响 新陈代谢. 因此，在喂养研究2（第2年）中，高饱和脂肪饮食 将使用添加和不添加大豆的。 两项喂养研究均将以随机、交叉、 控制喂养试验。 24名绝经前妇女将 为每项研究招募。 在基线期（1个月经周期）后， 其中关于日常饮食、运动习惯、月经周期和血清的数据， 将收集尿激素，这些妇女将被随机分配到 这两个研究饮食。 每名妇女将消耗两个月经周期的饮食 周期;经过一个月经周期的洗脱期，女性将跨越 另一种实验性饮食进行另外两个周期。 妇女将记录 在所有六个周期中每天测量基础体温，并进行连续 尿促黄体生成激素（LH）浪涌测试数天周期中; 此外，将连续抽血，并收集24小时尿液，每次两次 卵泡中期和黄体中期血、尿激素和性别周期 激素结合球蛋白分析，以确定不同类型的影响 饮食脂肪对荷尔蒙的影响 此外，在喂养研究2中， 将测量尿肌酐以确定代谢和排泄 模式. 这项随机临床试验扩展了我们对女性健康的了解， 提供了更准确的信息来了解：1）流行病学 饮食脂肪摄入与乳腺癌之间的联系; 2）使用 饮食暴露标志物;和3）乳腺风险的潜在指标， 进行癌症的一级预防监测。

DESCRIPTION: (Applicant's Description) Etiologic factors responsible for the development of sex steroid hormone-dependent cancer, such as breast cancer, are not fully understood, but level and type of dietary fat consumed have been hypothesized to contribute to the development of this cancer. Plant food intake has been consistently associated with lower risk for breast cancer. Specific non-nutrient phytochemicals, such as soy isoflavonoids, are similar in structure to sex steroid hormones and may therefore act in vivo to alter hormone metabolism and subsequent cancer risk. Because the majority of breast cancer cases appear to involve a strong hormonal component, it is probable that dietary fats and phytochemicals may influence this risk. The overall objective of this application is to explore the effects of varying types of dietary fat (thus, varying specific fatty acid content in the diet), but not the amount of total fat, on circulating steroid hormone (especially endogenous estrogen) in premenopausal women. Thus, in Feeding Study 1 (Year), two diets, both of which will provide 36 percent energy as fat and 15g dietary fiber (similar to American diet), will be used. The high saturated fat diet will pro-vide 23 percent of energy as saturated fat. The specific aim of this application is to determine whether serum concentrations and urinary excretion of sex hormones and binding proteins are influenced by type of fat, when fat intake is high and dietary fiber is moderate. Another objective of this project is to examine whether dietary soy may moderate the effect of dietary saturated fatty acids on hormones metabolism. Thus, in Feeding Study 2 (Year 2), the high saturated fat diet with and without added soy will be used. Both feeding studies will be implemented as randomized, crossover, controlling feeding trials. Twenty-four premenopausal women will be recruited for each study. After a baseline period (1 menstrual cycle), where data on usual diet, exercise habits, menstrual cycle, and serum and urinary hormones will be collected, the women will be randomized onto one of the two study diets. Each woman will consume that diet for two menstrual cycles; after a washout period of 1 menstrual cycle, a woman will cross over to the other experimental diet for another two cycles. Women will recorded basal body temperature daily for all six cycles, as well as perform serial urinary luteinizing hormone (LH) surge testing for several days mid-cycle; in addition, serial blood will be drawn and 24-h urine collected twice each cycle for midfollicular and midluteal serum and urinary hormone and sex hormone binding globulin analysis to determine the effects of varying types of dietary fat on hormone profiles. In addition, in Feeding Study 2, urinary isoflavonoids will be measured to determine metabolism and excretion patterns. This randomized clinical trial expands our knowledge of women's health and provides more precise information to understand: 1) the epidemiologic associations between dietary fat intake and breast cancer; 2) the use of diet exposure markers; and 3) potential indicators of breast risk which may be monitored for the primary prevention of cancer.