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Association of fetal hormone levels with stem cell potential: Evidence of prenatal influence on cancer risk
Intrauterine and perinatal factors have been linked to risk of testicular cancer and breast cancer in the offspring. In particular, many studies have provided evidence that supports the hypothesis of an intrauterine component in the origin of breast cancer. Human studies to examine the underlying biological mechanisms, however, have been limited. In Chapter 1, we review the likely role of stem cells in hormone-mediated carcinogenic process, particularly as intermediate steps between in utero exposure to hormones and breast cancer. We summarize also studies related to the assumptions of the hypothesis concerning in utero exposure. In Chapter 2 and 3, we report a reproducibility study for hormone assay and a population-based study that measured stem cell potential to explore mechanisms mediating the relation between in utero exposure to pregnancy hormones and cancer risk in the offspring. In these studies, we utilized umbilical cord blood collected two collection sites. Cord blood donors were 99 women, 18 years or older, who delivered a singleton birth. We assayed plasma concentrations of estradiol, unconjugated estriol, testosterone, progesterone, prolactin, sex-hormone binding globulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3). We observed in a reproducibility study that assays of these plasma hormones and binding proteins are reliable. For stem cell potential, we measured concentrations of CD34+, CD34 +CD38− cells, CD34+c-kit +. We applied linear regression analysis and controlled for maternal and neonatal characteristics. Data from two sample collection sites were analyzed separately and collectively. Based on the pooled data further taking into account cord sample collection sites, we found that CD34+ increases with increasing E3 (23% per SD increase, p = 0.02) and IGF-1 (25% per SD increase, p = 0.04). A similar increase was observed for IGFBP-3 (p = 0.05). E3, T, SHBG, and progesterone were weakly associated with CD34+CD38 −. These findings indicate that levels of growth factors and steroid hormones are associated with stem cell potential in human umbilical cord blood and point to a potential mechanism that may mediate the relation between in utero exposure to hormones and cancer risk in the offspring.
Public health|Cellular biology|Surgery|Oncology
Baik, Inkyung, "Association of fetal hormone levels with stem cell potential: Evidence of prenatal influence on cancer risk" (2005). Doctoral Dissertations Available from Proquest. AAI3179855.