IMPACT OF DIETARY FAT REDUCTION ON ESTROGEN METABOLISM

减少膳食脂肪对雌激素代谢的影响

• 批准号: 2105224
• 负责人: ELAINE N MEILAHN
• 金额: $ 1.94万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-22 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2105224
• 关键词: breast neoplasms; cancer prevention; cancer risk; cholesterol; dietary control; dietary lipid; estrogens; female; human subject; nutrition aspect of cancer; steroid hormone metabolism; urinalysis

The objective of the proposed study is to measure estrogen metabolites in urine samples from 250 healthy women before and after a low fat and cholesterol diet intervention and compare values with those from a control sample of 250 women. A high fat diet has been linked to excess risk of breast cancer. The underlying mechanisms for this relationship is unknown but is thought to involve an impact of dietary fat on estrogen metabolites are 2- and 16alpha-hydroxyestrone (16alpha-OHE1 may posses initiator and promoter activities in non-transformed mammary epithelial cells. 16alpha-hydroxylation is elevated in breast cancer patients, in women at high risk for breast cancer and in strains of mice susceptible to mammary tumors. The proposed study will determine whether a reduction in dietary fat intake results in a shift from 16alpha-OHE1 to 2- hydroxyestrone in the urine. Given that 16a-OHE1 is a potent estrogen, urinary levels could potentially serve as biomarkers for breast cancer risk and results of this study using a new assay on large population should help to elucidate the relationship of dietary fat to estrogen metabolism and breast cancer risk. The significance for research of the proposed study lies in its utilization of a newly developed noninvasive assay of estrogen metabolites in conjunction with a large carefully controlled randomized trial of dietary fat/cholesterol reduction in healthy normal women. The proposed study will provide an excellent basis on which to proceed with population-based studies on determinants of estrogen metabolism and biomarkers of breast cancer risk. Studies such as this also have a major public health significance in helping to evaluate general dietary recommendations directed at health promotion.

拟议研究的目的是测量雌激素代谢物 250 名健康女性在低脂饮食前后的尿液样本中 胆固醇饮食干预并将数值与来自 控制样本为 250 名女性。 高脂肪饮食与过量饮食有关 患乳腺癌的风险。 这种关系的基本机制 尚不清楚，但被认为涉及膳食脂肪对雌激素的影响 代谢物是 2- 和 16α-羟基雌酮（16α-OHE1 可能具有 非转化乳腺上皮中的引发剂和启动子活性 细胞。 乳腺癌患者的 16α-羟基化水平升高 乳腺癌高危女性和易感小鼠品系 到乳腺肿瘤。 拟议的研究将确定是否减少 膳食脂肪摄入量导致 16α-OHE1 转变为 2- 尿液中的羟基雌酮。 鉴于 16a-OHE1 是一种有效的雌激素， 尿液水平可能作为乳腺癌的生物标志物 本研究使用针对大量人群的新检测方法进行的风险和结果 应有助于阐明膳食脂肪与雌激素的关系 新陈代谢和乳腺癌风险。 本研究的研究意义在于 利用新开发的无创雌激素测定法 代谢物与大量仔细控制的随机对照研究相结合 健康正常女性减少膳食脂肪/胆固醇的试验。 这 拟议的研究将为继续进行提供良好的基础 基于人群的雌激素代谢决定因素研究 乳腺癌风险的生物标志物。 诸如此类的研究也有一个重大 帮助评估一般饮食的公共卫生意义 针对健康促进的建议。