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


CONCLUSIONS
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.
Savarese
Todd M
TM
Department of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Strohsnitter
William C
WC
Low
Hoi Pang
HP
Liu
Qin
Q
Baik
Inkyung
I
Okulicz
William
W
Chelmow
David P
DP
Lagiou
Pagona
P
Quesenberry
Peter J
PJ
Noller
Kenneth L
KL
Hsieh
Chung-Cheng
CC
D015703:Antigens, CD / Q000032:analysis; D001943:Breast Neoplasms / Q000196:embryology* / Q000453:epidemiology; D002455:Cell Division; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D005312:Fetal Blood / Q000737:chemistry* / Q000166:cytology; D006133:Growth Substances / Q000097:blood*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006728:Hormones / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D011247:Pregnancy
D015703:Antigens, CD; D006133:Growth Substances; D006728:Hormones; D007334:Insulin-Like Growth Factor I