Breast Cancer and the Environment Research Center

拟议的两个中心合作研究项目的总体目标是填补我们在宫内、出生后早期和青春期环境暴露对乳腺发育的细胞、分子、器官和人群水平的影响及其对未来乳腺癌风险的影响的具体知识空白。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 通过它们对子宫内至青春期乳房发育的影响而产生风险。这项研究利用一个独特的机会对500名4-11岁的多民族女孩进行跟踪调查，我们有广泛的宫内暴露和出生特征信息，并有机会前瞻性地收集她们童年时暴露的影响她们激素环境(雌激素、抗雌激素)和生长(饮食、运动、压力、胰岛素生物标记物)的机会，确定相关的基因多态并将其与青春期发育的时间联系起来。2)第二个合作研究项目将利用小鼠乳腺模型，通过体内和体外对孕酮作用机制的研究，重点研究PRA和PRB亚型的作用，以确定乳腺青春期发育和成熟的分子机制。在流行病学研究的同时，宫内、哺乳期和 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将被确定。最后，将确定这些环境暴露对随后发生乳腺癌的易感性的影响。最重要的假设是，在子宫内、哺乳期/配方奶喂养和哺乳期后/儿童期暴露于影响青春期时间的环境应激源。 发育和性成熟对乳腺癌风险的影响。我们特别假设，青春期发育加快和月经初潮提前通过增加终生孕激素与雌激素的共同作用而增加乳腺癌的风险。 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，并响应社区、信仰和倡导组织的意见，这些组织对乳腺癌和环境风险感兴趣。 为了最大限度地将新的调查结果转化为最有效的风险，社区外联和翻译核心将制定战略和工具，向妇女和女童以及社区利益攸关方和政策制定者传递信息。

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.