Environmental chemicals and postpubertal breast composition in a Latino cohort

 描述(申请人提供)：散发性乳腺癌是一种激素依赖性的恶性肿瘤，发病率稳步上升。虽然这一增长的原因尚不确定，但流行病学研究结果支持含有内分泌干扰物(EDCs)的环境污染物及其代谢物的重要作用。在过去的60年里，人们大量地将荷尔蒙活性的合成化学品引入环境中。因此，在生命过程中的关键机会窗口接触内皮细胞可能在改变乳腺癌易感性方面发挥作用。在这里，我们建议探索在青春期暴露于三种具有不同内分泌干扰途径的环境化合物，全氟辛酸丁酯(PFOA)、邻苯二甲酸苄酯(BBP)和玉米赤霉醇是否会改变乳房组成和/或乳腺癌的易感性。我们将在智利现有的400名拉丁裔女孩青春期队列的基础上，为她们 Tanner阶段4的乳房成分测量已经可用。我们建议扩大这一队列，在月经初潮两年后增加一项乳房成分评估，因为乳房密度从这一点跟踪到成年。我们建议研究三种化学物质，全氟辛酸、BBP和玉米赤霉醇单独和联合使用对这些拉丁裔女孩乳房组成的影响。为了探索青春期暴露于全氟辛酸、BBP和玉米赤霉醇是否会对乳腺生物学和致癌易感性产生有害影响，我们将研究暴露于这些化合物的大鼠乳腺的形态、转录组和肿瘤发生。我们的工作成果将通过社区外联向研究参与者的家庭成员和智利的社区成员传播。此外，我们将把这个项目和BCERP与美国的乳腺癌宣传联系起来，创造机会转化为促进健康的个人和政策变化。

 DESCRIPTION (provided by applicant): Sporadic breast cancer is a hormone dependent malignancy with a steadily increasing incidence. Although the reasons for this increase are uncertain, epidemiologic findings support an important role for environmental pollutants containing endocrine disrupting chemicals (EDCs) and their metabolites. The last six decades have witnessed a massive introduction of hormonally active synthetic chemicals into the environment. Therefore, exposure to EDCs at critical windows of opportunity during the life course may play a role in changing the susceptibility to breast carcinogenesis. Herein, we propose to explore whether exposure to three environmental compounds with different endocrine-disrupting pathways, butyl perfluorooctanoic acid (PFOA), benzyl phthalate (BBP), and Zeranol during the pubertal period will alter breast composition and/or the susceptibility to breast cancer. We will build on an existing puberty cohort of in 400 Latino girls in Chile for whom breast composition measurements at Tanner stage 4 are already available. We propose to extend this cohort to add a breast composition assessment two years after menarche as breast density tracks from this point into adulthood. We propose to study the influence of the three chemicals, PFOA, BBP, and Zeranol, individually and in combination, on breast composition in these Latino girls. To explore whether pubertal exposure to PFOA, BBP, and Zeranol has deleterious effects on mammary gland biology and susceptibility to carcinogenesis, we will study the morphology, transcriptome, and tumorigenesis of the rat mammary gland exposed to these compounds. Results from our work will be disseminated via community outreach to family members of study participants and community members in Chile. Furthermore, we will connect this project and BCERP with breast cancer advocacy in the United States, creating opportunities for translation into personal and policy change to promote health.