BA Public Health, National Taiwan U 1976
MPH Public Health, National Taiwan U 1978
MS Epidemiology, Harvard School of Public Health, 1980
ScD Epidemiology, Harvard School of Public Health, 1985
Cancer Epidemiology; Prenatal Origin of Cancer
Our laboratory area of interest is cancer epidemiology with research focusing on (1) prenatal origin of cancer risk, with special interest in the association of stem cells and perinatal factors with breast cancer risk, (2) gestational characteristics and maternal risk for breast and ovarian cancer, and (3) breast cancer risk factors for women of different ethnic backgrounds.
It has been hypothesized that the in utero environment and perinatal factors may influence cancer risk of the offspring later in life. We propose a stem cell burden hypothesis to explain how in utero and perinatal factors might impact lifetime breast cancer risk. Individuals with elevated in utero levels of growth factors and hormones will have relatively larger pools of stem cells, such as mammary stem cells, which would increase the probability that oncogenic mutations will occur in one of these cells, thus increasing the risk of getting breast cancer. Our laboratory has ongoing large population-based studies to examine in umbilical cord blood samples the relation between measurements of stem cell potential, such as hematopoietic stem cell, endothelial progenitor and mammary stem cell pools, and perinatal factors, such as endocrine mediators and birth size, with breast cancer risk. We have previously shown that cord blood plasma levels of insulin-like growth factor, estriol and insulin-like growth factor binding protein-3 are positively and significantly correlated with sub-populations of hematopoietic stem cells in normal pregnancies. Furthermore, there is also a positive association between birth weight and stem cell measurements. We have now expanded our studies to include pregnancies with different physiologic characteristics.
Studies using experimental animal models are also used to test the hypothesis that mammary gland density is determined in part by the number of mammary stem cells that arise during the in utero period and that the mammary stem cell pool is correlated with exposure to in utero mitogens. Recently, our laboratory has initiated studies to identify candidate biomarkers of reduced breast cancer risk using proteomic technologies. Understanding the mechanisms involved in the sequence of events between early-life exposures and adult cancer is important in cancer prevention research.