Early Life Exposures and Breast Density in Young Women

年轻女性的早期暴露和乳房密度

• 批准号: 9891025
• 负责人: JOANNE F DORGAN
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891025
• 关键词: 10 year old; 17 year old; Address; Adolescence; Adolescent; Adolescent obesity; Adult; Animals; Anthropometry; Biological Markers; Blood; Branched-Chain Amino Acids; Breast; Breast Cancer Risk Factor; Breast Epithelial Cells; Child; Childhood; Collection; Complex; Consumption; Development; Diet; Dietary Fats; Dietary Intervention; Distant; Enrollment; Environment; Epithelial Cell Proliferation; Exposure to; Fatty acid glycerol esters; Follow-Up Studies; Glutamates; Goals; Growth; Individual; Institute of Medicine (U.S.); Intake; Intervention; Intervention Studies; Isoleucine; Knowledge; LDL Cholesterol Lipoproteins; Leucine; Life; Life Cycle Stages; Linear Regressions; Long-Term Effects; Lysine; Mammary Duct; Mammary gland; Measures; Mediating; Mediation; Metabolic; Metabolic Pathway; Morphogenesis; Obesity; Overweight; Participant; Pathway Analysis; Pathway interactions; Phenotype; Physiological; Positioning Attribute; Predisposition; Prevention strategy; Puberty; Reporting; Research; Research Design; Resources; Risk; Safety; Serum; Sphingolipids; Time; Tissues; Unsaturated Fats; Valine; Woman; Youth; adult obesity; base; breast density; cancer risk; cohort; early life exposure; epidemiology study; follow-up; girls; innovation; intervention effect; malignant breast neoplasm; metabolomics; monounsaturated fat; novel; polyunsaturated fat; protective effect; saturated fat; young adult; young woman

Background: Adiposity in youth is inversely related to breast cancer risk throughout life, but the underlying mechanism is not understood. Breast density is one of the strongest breast cancer risk factors. In our ongoing research, adiposity in youth is strongly and significantly inversely associated with adult percent breast density as a consequence of heavier girls having less dense breast fibroglandular tissue. We also found youth saturated fat intake to be positively associated and unsaturated fat intake inversely associated with adult breast density. Objectives: The goal of this study is to identify physiological mechanisms that could mediate the associations of youth adiposity and dietary fat intake with breast density so targeted interventions can be developed. Specific Aims: Primary aims are to 1) identify metabolomic profiles in serum collected in youth associated with youth adiposity and young adult breast density; and 2) identify metabolomic profiles in serum collected in youth associated with youth fat subtype (saturated, polyunsaturated and monounsaturated fat) consumption and young adult breast density A secondary aim will formally evaluate mediation of associations of youth adiposity and dietary fat intake with breast density phenotypes by metabolites in serum collected in youth identified in aims 1 and 2. Study Design: We will use resources previously collected in the Dietary Intervention Study in Children (DISC) and DISC06 Follow-Up Study. DISC evaluated the safety and efficacy of a diet intervention to reduce LDL-cholesterol in children. 301 healthy girls 7-10 years old were enrolled in DISC and continued on study until they averaged 17 years old. Anthropometry was measured annually and dietary recalls and blood were collected biannually. DISC06 was conducted when participants were 25-29 years old to evaluate the longer-term effects of the intervention on biomarkers associated with breast cancer and included blood collection and assessment of anthropometry, diet and breast density. Approximately 300 participants will be included in analyses of associations of youth adiposity and diet with metabolites in serum collected during youth in DISC, while 182 participants will be included in analysis of associations with breast density phenotypes. Metabolomics profiles will be measured in stored serum collected during adolescence in DISC. Mixed effects linear regression will be used to identify individual metabolites associated with youth adiposity and dietary fat intake and adult breast density, while enrichment and pathway analysis will be used to identify relevant metabolic pathways. Significance: We are uniquely positioned to address an important and timely question that is highly innovative. Because it is a time of rapid proliferation of the mammary glands, adolescence may be a particularly vulnerable time for exposures related to breast cancer. Study results will increase understanding of adolescent determinants of breast density and identify physiological mechanisms underlying the association of adiposity and dietary fat intake in youth with adult breast density and possibly breast cancer risk. Metabolites identified could potentially be targeted as part of a novel preventive strategy.

背景：青少年肥胖与终生乳腺癌风险呈负相关，但潜在的肥胖风险 机制尚不清楚。乳房密度是最强的乳腺癌危险因素之一。在我们正在进行的 研究表明，青少年肥胖与成人乳房密度百分比呈强烈且显着的负相关 这是因为体重较重的女孩的乳房纤维腺组织密度较低。我们也找到了青春 饱和脂肪摄入量与成人呈正相关，不饱和脂肪摄入量与成人呈负相关 乳房密度。目的：本研究的目的是确定可以介导的生理机制 青少年肥胖和膳食脂肪摄入量与乳房密度之间的关系，因此可以采取有针对性的干预措施 发达。具体目标：主要目标是 1) 确定青少年收集的血清中的代谢组学特征 与青少年肥胖和年轻成人乳房密度有关； 2) 确定血清中的代谢组学特征 在与青少年脂肪亚型（饱和、多不饱和和单不饱和脂肪）相关的青少年中收集 消费和年轻成人乳房密度的次要目标将正式评估关联的中介作用 青少年肥胖和膳食脂肪摄入量与乳腺密度表型的关系（通过收集的血清中的代谢物进行） 目标 1 和 2 中确定的青少年。研究设计：我们将使用之前在《膳食》中收集的资源 儿童干预研究 (DISC) 和 DISC06 后续研究。 DISC 评估了以下药物的安全性和有效性 降低儿童低密度脂蛋白胆固醇的饮食干预。 301名7-10岁健康女孩参加DISC 并继续学习直到他们平均17岁。每年进行一次人体测量和饮食测量 每半年进行一次召回和血液采集。 DISC06 的参与者年龄为 25-29 岁， 评估干预措施对乳腺癌相关生物标志物的长期影响，包括 血液采集和人体测量、饮食和乳房密度的评估。约300名参与者将 纳入青少年肥胖和饮食与期间收集的血清中代谢物的关联分析 DISC 中的青少年，而 182 名参与者将被纳入与乳房密度关联的分析中 表型。代谢组学概况将在 DISC 中青春期收集的储存血清中进行测量。 混合效应线性回归将用于识别与青少年肥胖相关的个体代谢物 以及膳食脂肪摄入量和成人乳房密度，同时将使用富集和路径分析来确定 相关的代谢途径。意义：我们拥有独特的优势来解决重要而及时的问题 提出了一个极具创新性的问题。因为现在正是乳腺快速增生的时期， 青春期可能是特别容易接触乳腺癌的时期。研究结果将 增加对青少年乳房密度决定因素的了解并确定生理机制 青少年肥胖和膳食脂肪摄入量与成人乳房密度之间的关联，可能 乳腺癌风险。确定的代谢物可能成为新型预防策略的一部分。