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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

基本信息

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
项目类别：
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

项目摘要

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.