This proposal is Component 1 of a group of 3 Investigator- Initiated Research Project Grants (IRPG) that are submitted concurrently. The three projects address complementary aspects of the role of endogenous hormones in the etiology of the most common cancers specific to women-ovary, endometrium and breast. All studies are based on the same underlying population, obtained by combining three prospective cohort studies that are under way in New York, Umea (Sweden) and Milan (Italy). The present proposal addresses the potential role of a hyperandrogenic steroid profile in ovarian cancer. The second proposal focuses on hyperandrogenism and estrogens in endometrial cancer and the third (Component 3) on insulin IGF-I as the common determinant of hyperandrogenism in ovarian and endometrial cancers, and in breast cancer in young women. The study seeks to evaluate the hypothesis that the risk of epithelial ovarian cancer is increased in women who experience excessive ovarian androgen production, either as an etiologic factor per se, or as a reflection of chronic ovarian over- stimulation by gonadotropins. The primary aim is to determine whether pre-diagnostic blood levels of the major androgens of ovarian stromal origin, androstenedione and testosterone, are positively associated with the risk of epithelial ovarian cancer in both premenopausal and postmenopausal women. Secondary aim is to show that pre-diagnostic blood levels of SHBG are negatively associated with ovarian cancer in both premenopausal and postmenopausal women. A case-control study (approximately 143 cases and 286 controls) will be nested within the three joint cohort studies. Cases will be women diagnosed with epithelial ovarian cancer after entering any of the three cohort studies. Controls will be women randomly selected from among all eligible individuals from the same cohorts and matching a given case on specified criteria. The study duration will be three years.
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