Grant Number:	5R03CA082091-02 Interpret this number
Primary Investigator:	Baron, Andre
Organization:	Mayo Clinic
Project Title:	Serologic Serbbl in Healthy Women
Fiscal Year:	2000

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies in the United States. EOC usually is not diagnosed until a late stage, which results in a poor prognosis for the patient. Cost-effective, sensitive and specific screening methods to identify women who are at risk of developing EOC, and to detect early stages of EOC are, therefore, urgently needed. Multi-parity, lactation, and oral contraceptive use are known to decrease a woman's risk of EOC. These factors are believed to decreased the probability of cellular transformation by suppressing ovulation, wound healing, and proliferation of ovarian surface epithelium by altering gonadotropic and steroid hormone levels. Gonadotropic and steroid hormones regulate the expression of the erbB proto-oncogene receptor tyrosine kinases family. ErbB receptors play an important role in regulating the normal growth and differentiation of epithelial cells. Moreover, ErbB1 receptors are commonly amplified and/or over-expressed in ovarian neoplasms of epithelial origin, where increased signaling may contribute to cellular transformation. In addition to full-length ErbBl receptors, normal and malignant tissues produced "soluble" ErbB1 (sErbB1) analogs that have growth inhibitory properties in vitro. Recently, we have shown that serum sErbB1 levels differ significantly between healthy men (median = 24,512 fmol/ml) and women (median = 3,716 fmol/ml). Furthermore, studies with stage III or IV EOC patients indicate that serum sErbB1 levels are significantly lower in patients with this disease relative to healthy, age-matched women. Thus, decreased serum sErbB1 may contribute to the etiology of EOC. These observations have led us to hypothesize that decreased serum sErbB1 levels may be a risk factor for developing EOC and/or a potential diagnostic tumor biomarker of EOC. Since steroid hormones regulate erbB gene expression, and pregnancy, lactation, and oral contraceptive use affect circulating gonadotropic and steroid hormone levels, we predict that serum sErbB1 levels will be associated with aspects of a woman's reproductive history. The specific aims of this proposal are, therefore, to conduct a study of serum sErbB1 levels in healthy women: 1) during their menstrual cycle, 2) during oral contraceptive use, 3) during pregnancy, 4) during lactation, and 5) following menopause. This pilot project will establish baseline values for serum sErbB1 levels in healthy women, thereby, allowing us to obtain the information necessary to test the above hypotheses in future studies.





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