Early Determinants of Mammographic Density

乳房X光密度的早期决定因素

• 批准号: 7933188
• 负责人: MARY BETH TERRY
• 金额: $ 16.63万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7933188
• 关键词: Address; Adult; Age at Menarche; Archives; Biological; Biological Assay; Birth Order; Birth Weight; Blood Pressure; Body Size; Boston; Breast; Breast Cancer Epidemiology; Breast Cancer Risk Factor; California; Characteristics; Child; Child health care; Childhood; Complement; Data; Daughter; Development; Enrollment; Environment; Epidemiologic Studies; Epithelial; Estrogens; Exposure to; Family; Female; Fetal Growth; Future; Growth; Health; Height; High birth weight infant; Individual; Infant; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Interview; Laboratories; Lactation; Life; Literature; Low Birth Weight Infant; Malignant Neoplasms; Mammographic Density; Mammography; Maternal Age; Measurement; Measures; Mediating; Mediation; Menarche; Menopause; Mothers; Neonatal; New England; Pattern; Perinatal; Perinatal Exposure; Pre-Eclampsia; Predisposition; Pregnancy; Pregnant Women; Recruitment Activity; Reproductive History; Research Design; Research Personnel; Risk; Risk Factors; Sampling; Serum; Shapes; Siblings; Site; Socioeconomic Status; Somatomedins; Somatotropin; Structure; Testing; Testosterone; Third Pregnancy Trimester; Tissues; Weight; Weight Gain; Woman; aged; breast density; cancer risk; cohort; design; falls; fetal; high risk; malignant breast neoplasm; maternal cigarette smoking; maternal serum; novel; offspring; postnatal; programs; rapid growth; steroid hormone; success

DESCRIPTION (provided by applicant): Numerous studies have shown associations between markers of fetal growth and important domains of adult health. In particular, several recent studies suggest that high birth weight may be associated with an increased risk of breast cancer later in life. The existing literature on birth weight and breast cancer risk, while intriguing, falls short by its inability to address the following: (1) potential confounding by family factors (e.g., socioeconomic status); (2) the importance of and possible interaction with other measures of fetal growth; (3) the independent effect of maternal characteristics and exposures; (4) potential biological mechanisms; (5) the contribution of postnatal growth; and (6) mediation by adult risk factors. We will address these limitations by use of a novel study design examining the association of early life factors with mammographic density, a strong predictor of future breast cancer risk. Specifically, we will recruit a sibling sample of 325 female pairs (n=650) and a single child sample of 350 high birth-weight (>=4000g) females for a total of 1000 subjects. All females are offspring of pregnant women enrolled during 1959 to 1967 in two New England sites (Boston and Providence) of the National Collaborative Perinatal Project (NCPP) and in the Childhood Health and Development Study (CHDS). The sibling design will allow us to control for family effects such as socioeconomic status that may influence both birth-weight and adult risk factor patterns. Exposure information will be derived from prospectively collected pro and postnatal data on mothers, infants, and childhood growth. Maternal sera collected during the third trimester will be used to measure estrogen (El, E2, E3), and testosterone. Along with the mammogram, we will also collect adult risk factor data through interview and laboratory assays (including measures of IGF-I, IGFBP-3). We hypothesize that high birth weight, high placental weight, high placental/birth weight ratio, high maternal pregnancy weight gain, and high maternal estrogen levels will increase mammographic density in the daughters, and that maternal preeclampsia and higher levels of maternal testosterone will decrease mammographic density in the daughters. We will further examine whether any of these associations are mediated by childhood growth patterns and adult risk factors. This study will advance the literature on early determinants of breast cancer risk by directly addressing many of the limitations in the existing literature, allowing a more thorough inspection into what may shape early breast cancer susceptibility.

描述（由申请人提供）：许多研究表明，胎儿生长标记与成人健康重要领域之间的关联。特别是，最近的几项研究表明，高出生体重可能与以后生活中乳腺癌的风险增加有关。现有关于出生体重和乳腺癌风险的文献虽然令人着迷，但由于无法解决以下内容而缺乏：（1）家庭因素（例如，社会经济状况）的潜在混淆； （2）与其他胎儿生长量度的相互作用的重要性； （3）产妇特征和暴露的独立影响； （4）潜在的生物学机制； （5）产后生长的贡献； （6）由成人危险因素进行调解。我们将通过使用一项新的研究设计来解决这些局限性，该设计研究早期生命因素与乳腺X线摄影密度的关联，这是对未来乳腺癌风险的有力预测指标。具体而言，我们将招募325个女性对（n = 650）的同胞样本和一个350个高生物（> = 4000G）女性的单个儿童样本，总共1000名受试者。所有女性都是1959年至1967年在国家合作围产期项目（NCPP）和儿童健康与发展研究（CHDS）的两个新英格兰遗址（波士顿和普罗维登斯）的后代。同胞设计将使我们能够控制家庭效应，例如社会经济状况，可能会影响出生权重和成人风险因素模式。暴露信息将来自前瞻性收集的有关母亲，婴儿和儿童成长的产后数据。三个月期间收集的母体血清将用于测量雌激素（EL，E2，E3）和睾丸激素。除乳房X线照片外，我们还将通过访谈和实验室测定（包括IGF-I，IGFBP-3的量度）收集成人风险因素数据。我们假设高出生体重，高胎盘体重，高胎盘/出生体重比，高产妇怀孕体重增加和高母体雌激素水平将增加女儿的乳腺X线摄影密度，而母体先兆子痫和较高的母体睾丸激素水平会降低女儿的乳腺乳腺乳腺X线X型乳腺乳腺乳腺X线含量。我们将进一步研究这些关联中的任何一个是否是由儿童生长模式和成人危险因素介导的。这项研究将通过直接解决现有文献中的许多局限性来提高有关乳腺癌风险的早期决定因素的文献，从而对可能影响早期乳腺癌易感性的方法进行更彻底的检查。