Breast Cancer and the Environment Research Center

这两个拟议的中心合作研究项目的总体目标是填补我们在子宫内、产后早期和青春期环境暴露对细胞、分子、器官和群体水平上乳腺发育的影响及其对未来乳腺癌风险的影响方面的知识空白。这将通过以下方式实现：1) 一项流行病学研究，以确定可能影响乳腺癌的早期暴露 通过它们对青春期子宫内乳房发育的影响来评估风险。这项研究利用了一个独特的机会，对由 500 名 4-11 岁女孩组成的多种族队列进行随访，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荷尔蒙环境（雌激素、抗雌激素）和生长（饮食、运动、压力、胰岛素生物标志物）的童年暴露情况，识别相关的遗传多态性并将其与青春期发育时间联系起来。 2）第二个合作研究项目将利用小鼠乳腺模型，通过体内和体外研究黄体酮作用机制，重点关注PRA和PRB亚型的作用，确定乳腺青春期发育和成熟的分子机制。与流行病学研究并行，子宫内、哺乳期和哺乳期的影响 产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将被确定。最后，将确定这些环境暴露对随后乳腺肿瘤发展易感性的影响。总体假设是，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压力源 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会通过增加一生中与雌激素协同作用的黄体酮暴露量来增加乳腺癌风险。 为了促进将社区关切纳入中心研究项目，我们将与社区倡导者和其他利益相关者合作，并响应对乳腺癌和环境风险感兴趣的社区、信仰和倡导组织的意见。 为了将新发现优化转化为最有效的风险最小化，社区外展和翻译核心将开发战略和工具，将信息传递给妇女和女童以及社区利益相关者和决策者。

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.