Effects of diet on growth hormone-IGF-1 axis

本建议的具体目的是确定绝经前和绝经后妇女血液中胰岛素样生长因子- 1、胰岛素样生长因子结合蛋白-3和生长激素的水平是否受到低脂高碳水化合物饮食的影响。将采用的一般方法是对血液样本进行生长因子和激素检测，并对正在进行的多中心随机饮食干预试验的受试者进行食物记录的营养分析。这项试验的目的是验证一种假设，即低脂高碳水化合物饮食的干预将在乳房x光检查密度较大的女性中，在10年的时间内将乳腺癌的发病率降低29%。这项试验是解释性的，因为它试图确定饮食脂肪减少是否有降低乳腺癌发病率的生物学效应。为了实现这一目标，我们选择了乳腺癌风险增加的高积极性受试者作为参与者，我们为他们提供了高水平的饮食改变帮助，我们仔细跟踪他们以确保饮食改变的维持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4615名受试者的招募工作已于1998年11月完成。（随机抽取4693例）。参加试验的受试者的血液样本和食物记录将被用来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揭示饮食可能影响乳腺癌风险的潜在机制。虽然这不是本研究的目的，但试验的长期性质，对所有受试者的全面随访，以及对乳腺癌的完全确定，最终将允许在本研究中发现的任何血液标记物的变化与乳腺癌发病率的变化进行检验。

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.