title: Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study.
abstract: Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a nonsignificant decrease in risk for invasive [ORT3 vs. T1 : 0.79 (0.62-1.02); ptrend  = 0.07] and endometrioid tumors [ORT3 vs. T1 : 0.55 (0.28-1.07); ptrend  = 0.07]. The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis [ORT3 vs. T1 : 0.74 (0.57-0.96); ptrend  = 0.03]. Our study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.|Department of Medical Biosciences, Umeå University, Umeå, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Schock
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Renée T
authors.initials: RT
authors.lastname: Fortner
authors.affiliation: Unit of Child and Adolescent Health and Wellbeing, National Institute for Health and Welfare, Oulu, Finland.
authors.forename: Heljä-Marja
authors.initials: HM
authors.lastname: Surcel
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Grankvist
authors.affiliation: Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.|School of Public Health, University of Tampere, Tampere, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
authors.affiliation: School of Public Health, University of Tampere, Tampere, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.affiliation: Department of Medical Biosciences, Umeå University, Umeå, Sweden.|Public Health and Clinical Medicine: Nutritional Research, Umeå University, Umeå, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
mesh_terms: D000293:Adolescent; D000328:Adult; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016015:Logistic Models; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000378:metabolism*; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D010926:Placental Hormones / Q000378:metabolism*; D011247:Pregnancy; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D010926:Placental Hormones; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
keywords: IGF-I; ovarian neoplasms; placental GH; pregnancy; prospective studies