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    Correlation of umbilical cord blood hormones and growth factors with stem cell potential: implications for the prenatal origin of breast cancer hypothesis

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    Authors
    Savarese, Todd M.
    Strohsnitter, William C.
    Low, Hoi Pang
    Liu, Qin
    Baik, Inkyung
    Okulicz, William C.
    Chelmow, David P.
    Lagiou, Pagona
    Quesenberry, Peter J.
    Noller, Kenneth L.
    Hsieh, Chung-Cheng
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    UMass Chan Affiliations
    Department of Physiology
    Department of Neurology
    Department of Cancer Biology
    Cancer Center
    Document Type
    Journal Article
    Publication Date
    2007-05-16
    Keywords
    Antigens, CD
    Breast Neoplasms
    Cell Division
    Erythroid Progenitor Cells
    Female
    Fetal Blood
    Growth Substances
    Hematopoietic Stem Cells
    Hormones
    Humans
    Infant, Newborn
    Insulin-Like Growth Factor I
    Pregnancy
    Life Sciences
    Medicine and Health Sciences
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    Abstract
    INTRODUCTION: Prenatal levels of mitogens may influence the lifetime breast cancer risk by driving stem cell proliferation and increasing the number of target cells, and thereby increasing the chance of mutation events that initiate oncogenesis. We examined in umbilical cord blood the correlation of potential breast epithelial mitogens, including hormones and growth factors, with hematopoietic stem cell concentrations serving as surrogates of overall stem cell potential. METHODS: We analyzed cord blood samples from 289 deliveries. Levels of hormones and growth factors were correlated with concentrations of stem cell and progenitor populations (CD34+ cells, CD34+CD38- cells, CD34+c-kit+ cells, and granulocyte-macrophage colony-forming units). Changes in stem cell concentration associated with each standard deviation change in mitogens and the associated 95% confidence intervals were calculated from multiple regression analysis. RESULTS: Cord blood plasma levels of insulin-like growth factor-1 (IGF-1) were strongly correlated with all the hematopoietic stem and progenitor concentrations examined (one standard-deviation increase in IGF-1 being associated with a 15-19% increase in stem/progenitor concentrations, all P < 0.02). Estriol and insulin-like growth factor binding protein-3 levels were positively and significantly correlated with some of these cell populations. Sex hormone-binding globulin levels were negatively correlated with these stem/progenitor pools. These relationships were stronger in Caucasians and Hispanics and were weaker or not present in Asian-Americans and African-Americans. CONCLUSION: Our data support the concept that in utero mitogens may drive the expansion of stem cell populations. The correlations with IGF-1 and estrogen are noteworthy, as both are crucial for mammary gland development.
    Source
    Breast Cancer Res. 2007;9(3):R29. Link to article on publisher's site
    DOI
    10.1186/bcr1674
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/38380
    PubMed ID
    17501995
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1186/bcr1674
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