Early Life Exposures and Breast Density in Young Women

背景：青年肥胖与一生患乳腺癌的风险呈负相关，但潜在的 机制还不清楚。乳房密度是乳腺癌风险最大的因素之一。在我们正在进行的 研究表明，青年时期肥胖与成人的乳房密度呈显著负相关 这是因为体重较大的女孩的乳房纤维腺组织密度较低。我们也发现了青春 饱和脂肪摄入量与成人正相关，不饱和脂肪摄入量与成人负相关 乳房密度。目的：本研究的目的是确定可能调节心力衰竭的生理机制。 青年肥胖和膳食脂肪摄入量与乳房密度的关系因此可以进行有针对性的干预 发展起来的。具体目标：主要目标是：1)确定青年采集的血清中的代谢组谱 与青年肥胖和青年乳房密度有关；以及2)确定血清中的代谢组谱 青年时期收集的与青年脂肪亚型(饱和、多不饱和和单不饱和脂肪)有关的脂肪 消费和年轻人的乳房密度作为一个次要目标，将正式评估协会的调解 青年肥胖症和膳食脂肪摄入量与乳房密度表型的关系 目标1和目标2中确定的年轻人：研究设计：我们将使用之前在饮食中收集的资源 儿童干预研究(DISC)和DISC06随访研究。Disc评估了DISC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岁健康女孩参加了DISC 并继续学习，直到他们的平均年龄为17岁。每年测量一次人体尺寸和饮食 召回和血液每两年收集一次。DISC06是在参与者年龄在25-29岁到 评估干预对与乳腺癌相关的生物标记物的长期影响，包括 采集血液并评估人体测量、饮食和乳房密度。约300名参与者将 被纳入青年肥胖和饮食与血清代谢物的相关性分析中 盘中的青年，而182名参与者将被纳入与乳房密度的关联分析 表型。代谢组学图谱将在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确定与青年肥胖有关的个体代谢物 和膳食脂肪摄入量和成人乳房密度，而丰富和通径分析将被用来确定 相关的代谢途径。重要意义：我们处于独特的地位，能够及时解决重要的 这个问题很有新意。因为这是一个乳腺迅速增殖的时期， 青春期可能是与乳腺癌相关的暴露的特别脆弱的时期。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 青年肥胖症和膳食脂肪摄入量与成人乳房密度的关系 乳腺癌风险。作为新的预防策略的一部分，已确定的代谢物可能成为目标。

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.