Breast Cancer and the Environment Research Center

乳腺癌与环境研究中心

• 批准号: 7278300
• 负责人: SANDRA Z HASLAM
• 金额: $ 66.49万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-29 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7278300
• 关键词: Advocate; Affect; Age; Biological Markers; Birth; Breast; Characteristics; Childhood; Communities; Community Outreach; Development; Diet; Environment; Environmental Estrogen; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogens; Exposure to; Future; Genetic Polymorphism; Growth; Hormonal; In Vitro; Insulin; Knowledge; Mammary Neoplasms; Mammary gland; Menarche; Modeling; Molecular; Mus; Organ; Perinatal Exposure; Policy Maker; Population; Predisposition; Progesterone; Protein Isoforms; Puberty; Research; Research Project Grants; Risk; Role; Sexual Maturation; Stress; Time; Translations; Woman; advocacy organizations; base; cancer risk; cohort; diet and exercise; early onset; environmental stressor; feeding; follow-up; girls; in utero; in vivo; interest; malignant breast neoplasm; postnatal; tool

The overall objective of the two proposed Center Collaborative Research Projects is to fill specific gaps in our knowledge of the impact of in utero, early postnatal and pubertal environmental exposures on mammary gland development at the cellular, molecular, organ and population levels and their influence on future breast cancer risk. This will be accomplished through 1) an epidemiological study to identify early exposures that can influence breast cancer risk through their effects on breast development in utero through puberty. This study takes advantage of a unique opportunity to follow-up a multiethnic cohort of 500 girls ages 4-11 for whom we have extensive in utero exposures and birth characteristics information and the opportunity to prospectively collect their childhood exposures that influence their hormonal milieu (estrogens, antiestrogens) and growth (diet, exercise, stress, insulin biomarkers), identify relevant genetic polymorphisms and relate them to the timing of pubertal development. 2) The second collaborative research project will use the mouse mammary gland model to determine the molecular mechanisms of mammary gland pubertal development and maturation through in vivo and in vitro studies on the mechanism of progesterone action focusing on the roles of PRA and PRB isoforms. In parallel with the epidemiological studies, the effects of in utero, lactational and postnatal exposures to environmental estrogens, antiestrogens and diet on mammary gland pubertal development and maturation will be determined. Finally, the effect of these environmental exposures on subsequent susceptibility to mammary tumor development will be determined. The overarching hypothesis is that in utero, lactational/formula feeding and post-lactational/childhood exposures to environmental stressors that affect the timing of pubertal development and sexual maturation impact on breast cancer risk. We specifically hypothesize that accelerated pubertal development and early onset of menarche increase breast cancer risk by increasing lifetime exposure to progesterone acting in concert with estrogen. To facilitate the inclusion of community concerns into Center Research Projects we will partner with community advocates and other stakeholders, and be responsive to the input from community-based, faith-based and advocacy organizations that are interested in breast cancer and environmental risks. To optimize translation of new findings into the most effective risk minimization, the Community Outreach and Translation Core will develop strategies and tools to transmit the information to populations of women and girls, as well as community stakeholders and policy-makers.

这两个拟议的中心合作研究项目的总体目标是填补我们对子宫内、产后早期和青春期环境暴露在细胞、分子、器官和群体水平上对乳腺发育的影响及其对乳腺发育的影响的认识方面的具体空白。未来乳腺癌风险。这将通过1）流行病学研究来实现，以确定可能影响乳腺癌的早期暴露 通过影响子宫内乳房发育到青春期，这项研究利用了一个独特的机会，对500名年龄在4-11岁的女孩进行了多种族队列随访，我们对她们有广泛的子宫内暴露和出生特征信息，并有机会前瞻性地收集影响她们激素环境的儿童期暴露（雌激素、抗雌激素）和生长（饮食，运动，压力，胰岛素生物标志物），确定相关的遗传多态性，并将它们与青春期发育的时间相关联。2)第二个合作研究项目将使用小鼠乳腺模型，通过对孕酮作用机制的体内和体外研究，确定乳腺青春期发育和成熟的分子机制，重点是PRA和PRB亚型的作用。在流行病学研究的同时，还研究了子宫内、哺乳期和 将确定出生后暴露于环境雌激素、抗雌激素和饮食对乳腺青春期发育和成熟的影响。最后，将确定这些环境暴露对随后发生乳腺肿瘤易感性的影响。最重要的假设是，在子宫内，哺乳期/配方奶喂养和哺乳后/儿童期暴露于影响青春期时间的环境应激因素， 发育和性成熟对乳腺癌风险的影响。我们特别假设青春期发育加速和初潮提前通过增加与雌激素协同作用的孕酮的终生暴露而增加乳腺癌的风险。 为了促进社区关注纳入中心研究项目，我们将与社区倡导者和其他利益相关者合作，并对社区，信仰和倡导组织对乳腺癌和环境风险感兴趣的投入做出反应。 为了将新的调查结果最大限度地转化为最有效的风险最小化措施，社区外联和转化核心将制定战略和工具，向妇女和女孩以及社区利益攸关方和决策者传播信息。