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（适用提供）：妊娠和产前PAH以及其他环境暴露以及累积人类和动物数据的乳腺癌支持以下假设：乳腺癌风险在易感性的关键窗口中被修改。这些包括产前和妊娠窗户，在此期间，乳房的结构和功能变化，乳房细胞迅速增殖。哥伦比亚儿童环境健康中心（CCCEH）出生队列是世界上为数不多的人群之一，拥有广泛的生物测量和环境监测数据，这些数据反映了母亲和儿童产前期间在怀孕期间收集的当代环境。除了整个怀孕期间的尿液和血液中的多种样本外，母亲还穿着一个小的背包，这些背包在白天几天内白天有一个个人环境监测器，以测量个人空气污染的暴露。该队列仅由居住在纽约市的西班牙裔多米尼加和非裔美国人及其子女组成，这些妇女在1998年至2006年之间出生在布朗克斯或曼哈顿北部（n = 543位母亲，其中52.5％的母亲（n = 285）是母女daudds）。这些家庭反映了我们当地的社区，并代表了年轻女性乳腺癌炎症迅速增加的人口亚组。我们将收集现在青春期女孩（年龄范围10-16岁）及其母亲的乳房组织特征，人体测量法和生物测量的临床指标。人类的研究很少有测量对同一污染物的暴露，以便简单地评估其对母亲的乳腺癌风险和女儿的影响。我们将重点关注多环芳烃（PAH），IARC和美国EPA分类为可能的致癌物组合的副产品。我们将使人类研究与强大的动物实验相结合，研究了空中PAH在妊娠改变乳腺组织和全身性DNA甲基化和对母亲的DNA修复和凋亡重要的基因表达上的作用，其后代和壮大（项目2）。我们还将研究PAH在PPARγ基因调节中的作用，PPARγ基因调节，这对脂质代谢很重要，与乳腺癌的风险相关，以及在两种模型系统中较高PAH暴露的人类中甲基化的基因中，对动物和人类模型的检查乳腺组织改变。第3个项目通过在CCCEH社区外展和翻译核心建立建立，将我们的研究发现与有关我们的研究参与者的环境暴露和预防乳腺癌预防的信息融合在一起，并将其融合在一起。