PEDIGREE: Prenatal Environmental Determinants of InterGenerational Risk

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DESCRIPTION (provided by applicant): The investigators propose a unique study of human exposure to organchlorines during two critical windows of exposure for the breast: 1) pregnancy when preparation for lactation places the breast at risk for carcinogenesis in the mother and 2) the prenatal period when breast differentiation places the breast at risk for carcinogenesis in the daughter. There are few human studies where exposure to endocrine active compounds during these critical periods can be measured directly in relation to subsequent breast cancer risk. The proposed research addresses this gap and represents a novel and unique opportunity, efficiently using an existing cohort that spans two generations. The investigators will also develop the capacity for cohort members to participate as full research partners, enhancing the relevance and success of continuing breast cancer research in this unique study population. This study is made possible by a 50-year follow-up of the Child Health and Development Studies Pregnancy Cohort (CHDS). Maternal pregnancy serum samples were collected during peak exposure to organochlorine pesticides and polychlorinated biphenyls in the 1960's, prior to the ban on these chemicals. The proposed research funds organochlorine serum assays for recently diagnosed cases of breast cancer in mothers to extend the sample size for a prior published study of maternal breast cancer, collects 200 mammograms for daughters of mothers who have been diagnosed with breast cancer, assays 400 adult daughter specimens for DNA methylation, supports new data analysis to 1) test a novel hypothesis that maternal exposure during a critical window (prior to age 14) increases susceptibility of the fetus to the effects of environmental exposures in the womb; 2) test a well accepted hypothesis where data have not heretofore been available; that daughters of women who developed breast cancer are more susceptible to environmental exposures in the womb; and 3) examine the role of pregnancy hormone exposures in explaining observed organochlorine associations with breast cancer in mothers and age at menarche, mammographic density and DNA methylation of their daughters.