In Utero Organochlorine Exposure & Breast Density

描述（由申请人提供）：高乳腺密度与乳腺癌风险增加相关。这项流行病学研究将检验子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和单个多氯联苯同族物）会改变40-44岁妇女乳房密度的假设。研究人群（N=601）是儿童健康与发展研究（CHDS）的一个子集，这是一个加利福尼亚队列，从出生前开始跟踪了40多年。我们已经表明，在CHDS队列中，子宫内暴露于有机氯化合物是1)高且可变的，2)与成年女儿的生殖（怀孕时间）有关。拟议的研究将使用现有的关于40-44岁CHDS女儿乳腺密度和健康状况的数据，这些数据目前正在两个NIH资助的项目中收集（P01 AG023028-01, Ezra Susser， PI和RO1 CA104842-01， Mary Beth Terry， PI）。拟议的项目将资助产妇产前血清中有机氯的测定和相关的新数据分析。此外，CHDS的现有数据为检查重要的混杂或中介因素提供了机会，其中包括：1)女儿妊娠期间母亲雌激素和雄激素水平、母亲生殖和月经史、母亲体重、孕期体重增加、母亲吸烟和饮酒、女儿是否母乳喂养、女儿的宫内生长、婴儿期、童年早期和中期的前瞻性数据；2)女儿月经和生殖史、成人体型、健康状况和健康行为的回顾性和横断面资料。这将是第一次对人类乳房密度进行纵向研究，可以测量子宫内有机氯的暴露，此时胎儿可能非常脆弱。研究结果将有助于了解和预测出生在20世纪60年代的妇女患乳腺癌的风险，这些妇女在子宫内暴露于高水平的DDT。这些女性还没有达到患乳腺癌的高风险年龄。拟议的项目是对现有资源的有效利用，是一项独特的40年随访研究。

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.