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，发病率不断增加，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。过去六年见证了激素活性合成化学物质大量引入环境中，因此，在生命过程中的关键机会窗口接触 EDC 可能会在改变环境中发挥作用。在此，我们建议探讨在青春期接触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成分和/或。我们将以智利 400 名拉丁裔女孩的现有青春期队列为基础，研究她们对乳腺癌的易感性。 Tanner 第 4 阶段的乳房成分测量已经可用，我们建议在初潮两年后增加乳房成分评估，因为我们建议研究三种化学物质 PFOA 的影响。 BBP 和 Zeranol 单独或联合使用对这些拉丁裔女孩乳房成分的影响 为了探讨青春期接触 PFOA、BBP 和 Zeranol 是否对乳腺生物学和致癌易感性产生有害影响，我们进行了研究。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。在美国开展乳腺癌宣传活动，为转化为个人和政策变革以促进健康创造了机会。