Effects of diet on growth hormone-IGF-1 axis

该建议的具体目的是确定在绝经前和绝经后妇女中胰岛素样生长因子-I、胰岛素样生长因子结合蛋白-3和生长激素的血液水平是否受到低脂高碳水化合物饮食的影响。采用的一般方法是对血液样本进行生长因子和激素测定，并对食物记录进行营养分析，这些食物记录是从参加我们正在进行的多中心随机饮食干预试验的受试者中收集的。这项试验旨在验证一个假设，即在乳腺摄影密度广泛的妇女中，低脂高碳水化合物饮食干预将在10年内将乳腺癌的发病率降低29%。 该试验是解释性的，因为它试图确定在降低乳腺癌发病率方面，饮食脂肪减少是否有生物学效应。 为了实现这一目标，我们选择了积极性高的乳腺癌风险增加的受试者作为参与者，我们为他们提供了改变饮食的高水平帮助，我们仔细跟踪他们，以确保维持饮食变化和正确识别患乳腺癌的受试者，我们计划根据研究组和饮食依从性分析结果。 试验所需的4615名受试者的招募工作于1998年11月完成。 （共有4693人接受了随机分组）。入选试验的受试者的血液样本和食物记录将用于检验以下关于饮食干预对与乳腺癌风险相关的生长因子和激素的影响的假设。 通过饮食干预对这些因素的调节将表明饮食可能影响乳腺癌风险的潜在机制。 虽然不是这里提出的研究的目的，但试验的长期性质，所有受试者的完整随访以及乳腺癌的完全确定，最终将允许检查本研究中发现的血液标志物的任何变化与乳腺癌发病率的变化。

The specific aim of this proposal is to determine whether In premenopausal and postmenopausal women blood levels of Insulin like Growth Factor-I, Insulin like Growth Factor Binding Protein -3 and Growth hormone are influenced by a low-fat high- carbohydrate diet. The general method to be employed will be to perform assays for growth factors and hormone on blood samples, and nutrient analysis of food records, collected from subjects taking part in our ongoing multicentre randomized dietary intervention trial. This trial is designed to test the hypothesis that intervention with a low-fat high-carbohydrate diet will, in women with extensive mammographic densities, over a 10 year period reduce the incidence of breast cancer by 29 percent. The trial is explanatory in that it seeks to determine if there is a biological effect of dietary fat reduction in terms of a reduction in breast cancer incidence. To meet this goal we have selected as participants highly motivated subjects who are at increased risk of breast cancer, we have provided them with a high level of assistance in making a dietary alteration, we follow them carefully to ensure the maintenance of dietary change and the correct identification of subjects who develop breast cancer, and we plan to analyse the results according to study group and dietary compliance. Recruitment of the 4615 subjects required for the trial was completed in November 1998. (A total of 4693 were randomized). Blood samples and food records from subjects enroled in the trial will be used to test the hypotheses given below about the effects of dietary intervention on growth factors and hormones associated with breast cancer risk. Modulation of these factors by dietary intervention would indicate potential mechanisms by which diet may influence risk of breast cancer. Although not the purpose of the research proposed here, the long term nature of the trial, the complete follow-up of all subjects, and the complete ascertainment of breast cancer, will ultimately allow any changes in blood markers found in the present research to be examined in relation to changes in breast cancer incidence.