Breast Cancer and the Environment Research Center

乳腺癌与环境研究中心

• 批准号: 7489420
• 负责人: SANDRA Z HASLAM
• 金额: $ 64.92万
• 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/7489420
• 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.

这两个提议的中心协作研究项目的总体目标是填补我们对子宫内，早期和青春期环境对乳腺发展的影响，在细胞，分子，器官和人群水平及其对未来乳腺癌的影响下的影响。这将通过1）流行病学研究来实现，以识别可能影响乳腺癌的早期暴露 通过青春期对子宫内乳房发育的影响风险。 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青春期发展。 2）第二个协作研究项目将使用小鼠乳腺模型来确定通过体内乳腺青春期发育和成熟的分子机制，并在体外研究孕酮作用机制，重点是PRA和PRB同工型的作用。与流行病学研究并行，子宫，乳酸和 将确定产后暴露于环境雌激素，抗雌激素和饮食上的乳腺青春期发育和成熟的饮食。最后，将确定这些环境暴露对随后对乳腺肿瘤发育的敏感性的影响。总体假设是，在子宫里，泌乳/配方奶粉和乳制后/儿童期暴露于影响青春期时间的环境压力源 发育和性成熟对乳腺癌风险的影响。我们特别假设，通过增加与雌激素协同作用的孕酮的终生暴露，加速了青春期发育和初潮的早期发作，从而增加了乳腺癌的风险。 为了促进将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，并对对乳腺癌和环境风险感兴趣的基于社区，基于信仰和倡导组织的投入做出反应。 为了将新发现的翻译优化为最有效的风险最小化，社区外展和翻译核心将制定策略和工具，以将信息传输到妇女和女孩的人群以及社区利益相关者和政策制定者。