In Utero Organochlorine Exposure & Breast Density

描述(申请人提供)：乳房密度高与乳腺癌风险增加有关。这项流行病学研究将检验这样一种假设，即宫内暴露于环境内分泌活性化合物(有机氯化合物、p，p‘-DDT、p，p’-DDE、o，p‘-DDT和个别多氯联苯同系物)会改变40-44岁女性的乳房密度。研究人群(N=601)是儿童健康和发展研究(CHDS)的子集，CHDS是加利福尼亚州的一个队列，从出生前就开始跟踪调查了40多年。我们已经证明，在宫内接触有机氯化合物在CHDS队列中是高度和可变的，以及2)与成年女儿的生殖(怀孕时间)有关。这项拟议的研究将使用年龄在40-44岁的CHDS女儿的乳房密度和健康状况的现有数据，这些数据目前正在NIH资助的两个项目中收集(P01 AG023028-01，Ezra Susser，PI和RO1 CA104842-01，Mary Beth Terry，PI)。拟议的项目将为孕妇产前血清有机氯检测和相关新数据分析提供资金。此外，CHDS的现有数据为研究重要的混淆或中介因素提供了机会，这些因素包括1)关于女儿怀孕期间母亲的雌激素和雄激素水平、母亲的生殖和月经史、母亲的体重和怀孕体重增加、母亲吸烟和酗酒、女儿是否母乳喂养、女儿的宫内发育、婴儿期、儿童早期和中期的前瞻性数据；和2)关于女儿的月经和生育史、成年体重、健康和健康行为的回顾和横断面数据。这将是第一项关于人类乳房密度的纵向研究，可以测量胎儿在宫内暴露于有机氯的情况，当时胎儿可能非常脆弱。研究结果将有助于了解和预测出生于60年代的S妇女患乳腺癌的风险，她们在宫内暴露于高水平的滴滴涕。这些妇女还没有达到乳腺癌高风险的年龄。拟议的项目是对现有资源的有效利用，以进行一项独特的40年后续研究。

DESCRIPTION (provided by applicant): High breast density is associated with increased risk of breast cancer. This epidemiological study will test the hypothesis that in-utero exposure to environmental endocrine-active compounds (organochlorine compounds, p,p'-DDT, p,p'-DDE, o,p'-DDT and individual PCB congeners) alters breast density in women measured at 40-44 years of age. The study population (N=601) is a subset of the Child Health and Development Studies (CHDS), a California cohort that has been followed for more than 40 years, beginning before birth. We have already shown that in-utero exposures to organochlorine compounds are 1) high and variable in the CHDS cohort and 2) are associated with reproduction (time to pregnancy) in adult daughters. The proposed study will use existing data on breast density and health status in CHDS daughters at age 40-44 years of age, which are currently being collected in two NIH funded projects (P01 AG023028-01, Ezra Susser, PI and RO1 CA104842-01, Mary Beth Terry, PI). The proposed project would fund assays of maternal prenatal serum for organochlorines and related new data analysis. In addition, existing data in the CHDS provide an opportunity to examine important confounding or mediating factors, which include 1) Prospective data on maternal estrogen and androgen levels during the daughter's gestation, maternal reproductive and menstrual history, maternal body mass, and pregnancy weight gain, maternal smoking and alcohol use, whether daughter was breastfed, daughter's growth in-utero, infancy, early and and middle childhood; and 2) Retrospective and cross-sectional data on daughter's menstrual and reproductive history, adult body size, health and health behaviors. This would be the first longitudinal study of human breast density that can measure exposure to organochlorines in-utero, when the fetus may be highly vulnerable. Findings will be relevant to understanding and predicting the breast cancer risk of women born in the 1960's, who were exposed to high levels of DDT in-utero. These women have not yet achieved the age of high breast cancer risk. The proposed project is an efficient use of existing resources for a unique 40-year follow-up study.