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：年轻人的肥胖与一生中的乳腺癌风险成反比，但基础 机制尚不理解。乳房密度是最强的乳腺癌危险因素之一。在我们正在进行的中 研究，年轻人的肥胖与成人乳房密度的强烈和显着相关 由于较重的女孩的胸部纤维纤维兰布组织较少。我们还找到了青年 饱和脂肪的摄入量与成人呈正相关和不饱和脂肪的摄入量 乳房密度。目标：这项研究的目的是确定可以介导的生理机制 青少年肥胖和饮食脂肪摄入与乳房密度的关联，因此可以进行针对性的干预措施 发达。具体目的：主要目的是1）确定青年收集的血清中代谢组谱 与青年肥胖和年轻成人乳房密度相关； 2）识别血清中的代谢组谱 在与青年脂肪亚型相关的青年中收集（饱和，多不饱和和单不饱和脂肪） 消费和年轻的成人乳房密度次要目标将正式评估关联的调解 在收集的血清中代谢物的青年肥胖和饮食脂肪摄入乳房密度表型 在目标1和2中确定的青年研究设计：我们将使用先前在饮食中收集的资源 儿童干预研究（DISC）和DISC06随访研究。光盘评估了安全性和功效 饮食干预以减少儿童的LDL-胆固醇。 301个7-10岁的健康女孩已入学 并继续学习，直到他们平均17岁为止。每年测量人体测量法和饮食 召回和血液每两年收集。当参与者25-29岁时进行迪斯特06 评估干预对与乳腺癌相关的生物标志物的长期影响，并包括 人体测量法，饮食和乳房密度的血液收集和评估。大约300名参与者将 被包括在青年肥胖和饮食与代谢物的关联分析中 椎间盘中的青年，而乳房密度的协会分析将包括182名参与者 表型。代谢组学谱将在青春期在椎间盘期间收集的血清中进行测量。 混合效应线性回归将用于识别与青年肥胖相关的单个代谢产物 以及饮食脂肪的摄入量和成人乳房密度，而富集和途径分析将用于识别 相关的代谢途径。意义：我们有独特的位置来解决一个重要及时的问题 高度创新的问题。因为这是乳腺快速增殖的时期，所以 青春期可能是与乳腺癌相关的暴露时间特别脆弱的时间。研究结果将 增加对乳房密度的青少年决定因素的理解并确定生理机制 青年人与成人乳房密度的肥胖性和饮食脂肪摄入量的关联以及可能 乳腺癌风险。所鉴定的代谢产物可能是一种新型预防策略的一部分。