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. ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA120061-04
Application #
7488771
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Kasten-Sportes, Carol H
Project Start
2006-09-01
Project End
2011-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
4
Fiscal Year
2008
Total Cost
$386,251
Indirect Cost
Name
German Cancer Research Center
Department
Type
DUNS #
325989556
City
Heidelberg
State
Country
Germany
Zip Code
69120
Ose, Jennifer; Poole, Elizabeth M; Schock, Helena et al. (2017) Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium. Cancer Res 77:3951-3960
Ose, Jennifer; Schock, Helena; Poole, Elizabeth M et al. (2017) Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes: A collaborative re-analysis from the Ovarian Cancer Cohort Consortium. Cancer Causes Control 28:429-435
Schock, Helena; Zeleniuch-Jacquotte, Anne; Lundin, Eva et al. (2016) Hormone concentrations throughout uncomplicated pregnancies: a longitudinal study. BMC Pregnancy Childbirth 16:146
Schock, Helena; Fortner, Renée T; Surcel, Heljä-Marja et al. (2015) Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study. Int J Cancer 137:439-47
Toriola, Adetunji T; Tolockiene, Egle; Schock, Helena et al. (2014) Free ?-human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer. Future Oncol 10:377-84
Schock, H; Lundin, E; Vääräsmäki, M et al. (2014) Anti-Mullerian hormone and risk of invasive serous ovarian cancer. Cancer Causes Control 25:583-9
Schock, Helena; Surcel, Heljä-Marja; Zeleniuch-Jacquotte, Anne et al. (2014) Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer. Endocr Relat Cancer 21:831-44
Lukanova, Annekatrin; Surcel, Helja-Marja; Lundin, Eva et al. (2012) Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer. Int J Cancer 130:910-20
Toriola, Adetunji T; Lundin, Eva; Schock, Helena et al. (2011) Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer. Cancer Epidemiol Biomarkers Prev 20:1798-801
Chen, Tianhui; Surcel, Helja-Marja; Lundin, Eva et al. (2011) Circulating sex steroids during pregnancy and maternal risk of non-epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 20:324-36

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