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Association of Fetal Hormone Levels with Stem Cell Potential: Evidence for Early Life Roots of Human Cancer

¹ Cancer Research Center and Department of Cancer Biology and ² Department of Physiology, ILAT Steroid RIA Laboratory, University of Massachusetts Medical School; ³ Department of Obstetrics and Gynecology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts; ⁴ Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts; ⁵ Division of Hematology and Oncology, Massachusetts General Hospital; ⁶ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; ⁷ Division of Hematology, University of Washington, Seattle, Washington; ⁸ Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Athens, Greece; and ⁹ Department of Research, Roger Williams Medical Center, Providence, Rhode Island

Requests for reprints: Chung-Cheng Hsieh, Division of Biostatistics and Epidemiology, Department of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, LRB 427, Worcester, MA 01605. Phone: 508-856-4780; Fax: 508-856-2212; E-mail: chung.hsieh{at}umassmed.edu

Intrauterine and perinatal factors have been linked to risk of childhood leukemia, testicular cancer, and breast cancer in the offspring. The pool of stem cells in target tissue has been suggested as a critical factor linking early life exposures to cancer. We examined the relation between intrauterine hormone levels and measurements of stem cell potential in umbilical cord blood. Cord blood donors were 40 women, ages 18 years, who delivered, from August 2002 to June 2003, a singleton birth after a gestation of at least 37 weeks. We assayed plasma concentrations of estradiol, unconjugated estriol, testosterone, progesterone, prolactin, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), and IGF binding protein-3. For stem cell potential, we measured concentrations of CD34⁺ and CD34⁺CD38^– cells and granulocyte-macrophage colony-forming unit (CFU-GM). We applied linear regression analysis and controlled for maternal and neonatal characteristics. We found strong positive associations between IGF-I and stem cell measures, 1 SD increase in IGF-I being associated with a 41% increase in CD34⁺ (P = 0.008), a 109% increase in CD34⁺CD38^– (P = 0.005), and a 94% increase in CFU-GM (P = 0.01). Similar associations were observed for IGF binding protein-3. Among steroid hormones, estriol and testosterone were significantly positively associated with CD34⁺ and CFU-GM. These findings indicate that levels of growth factors and hormones are strongly associated with stem cell potential in human umbilical cord blood and point to a potential mechanism that may mediate the relationship between in utero exposure to hormones and cancer risk in the offspring.

Key Words: cancer risk • growth factors • hormones • in utero exposure • stem cells potential

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