Pregnancy and Prenatal PAHs and other Environmental Exposures and Breast Cancer

怀孕和产前多环芳烃和其他环境暴露与乳腺癌

• 批准号: 9145662
• 负责人: RACHEL L MILLER
• 金额: $ 90.79万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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/9145662
• 关键词: Address; Adolescence; Adolescent; Adult; African American; Age; Age-Years; Air Pollution; Animal Experiments; Animals; Anthropometry; Apoptosis; Aromatic Polycyclic Hydrocarbons; Biological Models; Birth; Blood; Body Size; Body mass index; Breast; Breast Cancer Prevention; Breast Cancer Risk Factor; Candidate Disease Gene; Carcinogens; Catchment Area; Cells; Characteristics; Child; Clinical; Cohort Studies; Communities; Community Medicine; Community Outreach; Complement; DNA Methylation; DNA Repair; Data; Daughter; Dominican; Educational Materials; Enrollment; Ensure; Environment; Environmental Carcinogens; Environmental Exposure; Environmental Health; Environmental Monitoring; Environmental Pollutants; Epigenetic Process; Evaluation; Exposure to; Family; Family Practice; Female; Female Adolescents; Gene Expression; Gene Expression Regulation; Generations; Genes; Health; Herbert Irving Comprehensive Cancer Center; Hispanics; Hour; Human; Incidence; Individual; International Agency for Research on Cancer; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary gland; Mammography; Measures; Methods; Methylation; Modeling; Mothers; Mus; New York City; Obesity; Optics; Outcome; PPAR gamma; Participant; Population; Postpartum Period; Predisposition; Pregnancy; Premenopause; Prevention strategy; Primary Prevention; Proliferating; Research; Risk; Role; Sampling; Science; Source; Spectrum Analysis; Structure; Subgroup; Teenagers; Time; Tissues; Translations; United States Environmental Protection Agency; Universities; Urine; Woman; air monitoring; animal data; breast density; cancer prevention; cancer risk; cohort; combustion product; experience; girls; human data; human study; interdisciplinary approach; lipid metabolism; malignant breast neoplasm; mouse model; next generation sequencing; novel; offspring; peripheral blood; pollutant; postnatal; prenatal; prenatal exposure; research study; screening; young adult; young woman

 DESCRIPTION (provided by applicant): Pregnancy and Prenatal PAHs and other Environmental Exposures and Breast Cancer Accumulating human and animal data support the hypothesis that breast cancer risk is modified during key windows of susceptibility. These include the prenatal and pregnancy windows, during which time the breast changes in structure and function and breast cells rapidly proliferate. The Columbia Center for Children's Environmental Health (CCCEH) birth cohort is one of the few cohorts in the world with extensive biospecimens and environmental monitoring data that are reflective of the contemporary environment collected during the pregnancy time period for mothers and during the prenatal period for children. In addition to multiple samples of urine throughout pregnancy and blood at the time of delivery, mothers wore a small backpack containing a personal ambient air monitor during the daytime hours for several days to measure personal air pollution exposures. The cohort is comprised exclusively of Hispanic Dominican and African-American women residing in New York City and their children, who were born in the Bronx or Northern Manhattan between 1998 and 2006 (N=543 mothers of whom 52.5% (N=285) are mother-daughter dyads). These families reflect our local community, as well as represent the population subgroups experiencing a rapidly increasing breast cancer incidence in young women. We propose to build on this unique birth cohort specifically by measuring breast tissue characteristics and breast density, a strong intermediate marker of breast cancer risk through optical spectroscopy (OS) for all mothers and daughters and mammography for mothers over 40 years of age (Project 1). We will collect clinical measures of breast tissue characteristics, anthropometry and biospecimens in the now adolescent girls (age range 10-16 years) and their mothers. There are few human studies in which exposures to the same pollutants have been measured to allow for simultaneous evaluation of their effect on both the mother's breast cancer risk and that of her daughter. We will focus on Polycyclic Aromatic Hydrocarbons (PAH), by-products of combustion classified as possible carcinogens by IARC and the US EPA. We will couple our human study with robust animal experiments investigating the role of airborne PAH during gestation on altered mammary tissue and systemic DNA methylation and expression of genes important to DNA repair and apoptosis in mothers, their offspring, and their grandoffspring (Project 2). We also will investigate the role of PAH on PPARγ gene regulation, a gene important to lipid metabolism and associated with breast cancer risk, as well as examine mammary tissue alterations in both the animal and human models and compare genes that are methylated in humans with higher PAH exposure across both model systems. Project 3 ties together both projects by building on the CCCEH Community Outreach and Translation Core to integrate our research findings with messages about environmental exposures and breast cancer prevention in our study participants and larger community in our Herbert Irving Comprehensive Cancer Center (HICCC) and Columbia University catchment area.

 描述（由申请人提供）：怀孕和产前多环芳烃以及其他环境暴露和乳腺癌 积累的人类和动物数据支持这样的假设：乳腺癌风险在关键的易感窗口期发生变化，其中包括产前和怀孕窗口期。乳房结构和功能的变化以及乳房细胞的快速增殖 哥伦比亚儿童环境健康中心 (CCCEH) 出生队列是世界上少数拥有大量生物样本的队列之一。母亲在怀孕期间和儿童产前期间收集的反映当代环境的环境监测数据 除了整个怀孕期间的多个尿液样本和分娩时的血液样本外，母亲们还背着一个小背包，其中装有物品。该队列由居住在纽约市的西班牙裔多米尼加裔和非裔美国妇女及其出生在布朗克斯或曼哈顿北部的孩子组成。 1998年至2006 年（N=543 名母亲，其中 52.5%（N=285）是母女二人组）。这些家庭反映了我们当地的社区，也代表了年轻女性乳腺癌发病率迅速增加的人群。在此独特的出生队列的基础上，特别通过测量乳腺组织特征和乳腺密度，通过对所有母亲和女儿进行光谱 (OS) 测量乳腺癌风险的强中间标记，并对 40 岁以上的母亲进行乳房 X 光检查（项目 1）我们将收集目前青春期女孩（年龄范围 10-16 岁）及其母亲的乳腺组织特征、人体测量学和生物样本的临床测量数据。很少有人类研究测量过相同污染物的暴露情况。为了同时评估它们对母亲和女儿患乳腺癌风险的影响，我们将重点关注多环芳烃 (PAH)，即被 IARC 列为可能致癌物的燃烧副产品。我们将把我们的人体研究与强有力的动物实验结合起来，研究妊娠期间空气中的多环芳烃对改变乳腺组织和全身 DNA 甲基化以及对母亲、其后代和孙辈 DNA 修复和细胞凋亡重要的基因表达的作用。 （项目 2）我们还将研究 PAH 对 PPARγ 基因调控的作用，PPARγ 是一种对脂质代谢很重要且与乳腺癌风险相关的基因，并检查动物和人类模型中乳腺组织的变化并比较基因。项目 3 在 CCCEH 社区外展和翻译核心的基础上将这两个项目结合在一起，将我们的研究结果与我们的研究参与者和更大范围内的环境暴露和乳腺癌预防信息相结合。我们的赫伯特·欧文综合癌症中心 (HICCC) 和哥伦比亚大学学区的社区。