Grant Number:	5R01CA090902-04 Interpret this number
Primary Investigator:	Hsieh, Chung-Cheng
Organization:	Univ Of Massachusetts Med Sch Worcester
Project Title:	Stem Cells and Perinatal Factors for Breast Cancer Risk
Fiscal Year:	2005

DESCRIPTION (provided by applicant): This study proposes to examine whether hormone levels in human umbilical cord blood are associated with measurements of stem cell potential and expression of Bcl-2 family proteins indicating levels of apoptotic activity. Measurements of stem cells and Bcl-2 apoptosis will be further examined to see if they correlate with birth weight as an indicator of fetal growth. The study is based on the hypothesis that cancer risk can be influenced in part by the hormonal environment in utero and that cancer risk is proportional to the number of primitive proliferating stem cells. Umbilical cord blood from 300 donors will be obtained from singleton birth, full-term, and low-risk deliveries at hospitals affiliated with the American Red Cross Cord Blood Program. Hormones and other growth factors including estradiol, estriol, progesterone, prolactin, sex-hormone binding globulin (SHIBG), testosterone, insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3) will be assayed in cord blood samples. We will measure the total number of nucleated cells, number of cells per volume expressing CD34 protein on the cell surface as well as CD34+/CD38, CD34+/c-kit, and CD45/GlyA sub-population cells, and the number of colony-forming-unit granulocytes and macrophages (CFU-GM) as laboratory parameters for primitive proliferating stem cells. Among Bcl-2 family proteins we will measure the expression of Bcl-2, Bcl-xL, Bax, and Bad to construct an overall apoptotic index. We will apply regression analysis treating as outcome variables each measurement of stem cell potential and Bcl-2 apoptotic index and as predictor variables hormone levels, controlling for maternal and neonatal characteristics. Stem cell measurements and index of Bcl-2 apoptotic expressions will be further examined as predictors of birth weight. The study seeks to obtain information on parameters of perinatal cell proliferation relevant to intervening steps between intrauterine hormone exposure and subsequent cancer risk.