Environmental chemicals and postpubertal breast composition in a Latino cohort

拉丁裔人群中的环境化学物质和青春期后乳房成分

• 批准号: 9471887
• 负责人: JULIA Green BRODY
• 金额: $ 89.18万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9471887
• 关键词: Environmental; chemicals; postpubertal; breast; composition

 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.

 描述（由申请人提供）：散发性乳腺癌是一种激素依赖性恶性肿瘤，发病率稳步上升。尽管这种增加的原因尚不确定，但流行病学研究结果支持含有内分泌干扰化学物质 (EDC) 及其代谢物的环境污染物的重要作用。在过去的六年里，荷尔蒙活性合成化学品被大量引入环境中。因此，在生命过程中的关键机会窗口接触 EDC 可能在改变乳腺癌易感性方面发挥作用。在此，我们建议探讨青春期期间暴露于三种具有不同内分泌干扰途径的环境化合物：丁基全氟辛酸（PFOA）、邻苯二甲酸苄酯（BBP）和玉米赤霉醇是否会改变乳房成分和/或对乳腺癌的易感性。我们将以智利现有的 400 名拉丁裔女孩为对象进行青春期队列研究 Tanner 第 4 阶段的乳房成分测量已经可用。我们建议扩展该队列，在初潮两年后添加乳房成分评估，因为乳房密度从此时开始一直跟踪到成年期。我们建议研究 PFOA、BBP 和 Zeranol 三种化学物质（单独或组合）对这些拉丁裔女孩乳房成分的影响。为了探讨青春期暴露于 PFOA、BBP 和 Zeranol 是否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。我们的工作结果将通过社区外展传播给研究参与者的家庭成员和智利的社区成员。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，为转化为个人和政策变革以促进健康创造机会。