A pregnancy completed to term is the strongest known protective factor for ovarian cancer. Older age at the end of child-bearing confers greater protection than younger age and it was proposed that pregnancy may clear the ovaries from cells that have undergone malignant transformation - the wash-out hypothesis. Progesterone is the most likely hormone candidate to mediate the beneficial effect of pregnancy. In a case control study (1,827 cases, 3,654 controls), nested within two large cohorts in Finland and Sweden, we will explore the associations between progesterone and 17alpha-OH progesterone (marker of corpus luteum function and correlate of ovarian synthesis of progesterone) in stored specimens obtained during the first trimester of a last, full-term pregnancy and the subsequent risk of invasive or borderline ovarian cancer in the mother.
Specific aims are the following: 1). To investigate prospectively the association of circulating progesterone and 17a-OH progesterone during the first trimester of a last full-term pregnancy with risk of epithelial ovarian cancer in the mother and to explore the effect of age at last full-term pregnancy on these associations. 2). To explore the above hormone-cancer associations according to the histological sub-type of both invasive and borderline epithelial ovarian malignancies. Additionally, the large Nordic cohorts offer the opportunity to address the role of two groups of hormones that have been associated with increased ovarian cancer risk. Two more specific aims are proposed: 3). To examine prospectively the association of IGF-I, IGFBP-3 and placental GH during early pregnancy with maternal risk of ovarian cancer overall, and in subgroups defined by the histological types of the tumors. 4). To examine prospectively the association of testosterone, androstenedione and SHBG during pregnancy with maternal risk of ovarian cancer overall, and in subgroups defined by the histological types of the tumors. The proposed study will be one of the largest studies on ovarian cancer conducted to date. It will gather important new data concerning the role of progesterone in the protection afforded by pregnancies, and the role of the IGF-system and androgens, on ovarian cancer risk. Observations from this study may lead to a better understanding of disease pathogenesis, and, ultimately to development of preventive interventions.
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