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Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. German Cancer Research Center, Heidelberg.
German Cancer Research Center, Heidelberg.
National Institute for Health and Welfare, Oulu, Finland.
Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
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2015 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 2, 439-447 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2015. Vol. 137, no 2, 439-447 p.
Keyword [en]
placental GH, IGF-I, ovarian neoplasms, pregnancy, prospective studies
National Category
Cancer and Oncology Medical Bioscience
Research subject
Pathology
Identifiers
URN: urn:nbn:se:umu:diva-102011DOI: 10.1002/ijc.29387ISI: 000354287600018PubMedID: 25516257OAI: oai:DiVA.org:umu-102011DiVA: diva2:806410
Note

Article first published online: 17 DEC 2014

Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Hormone concentrations during pregnancy and maternal risk of epithelial ovarian cancer
Open this publication in new window or tab >>Hormone concentrations during pregnancy and maternal risk of epithelial ovarian cancer
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The aim of this thesis was to study the relationship of pre-diagnostic circulating concentrations of sex steroid hormones (androgens, estradiol, 17-hydroxyprogesterone, and progesterone), growth factors (insulin-like growth factor-I (IGF-I), placental growth hormone (GH)), sex hormone binding globulin (SHBG), and anti-Müllerian hormone (AMH) with risk of epithelial ovarian cancer (EOC) overall, and by tumor invasiveness and histology. A longitudinal study was used to assess patterns of hormonal changes during a single pregnancy, and in two consecutive pregnancies.

Materials & Methods: A case-control study was nested within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort. A total of 1 052 EOC cases were identified through linkages with the cancer registries in both countries. For each case, 2-3 controls were selected. Cases and controls were matched on cohort, age and date at blood draw, as well as for parity at blood draw and at diagnosis (n=2 695). Odds ratios (OR) and corresponding 95% confidence intervals [CI] were estimated using conditional logistic regression. The longitudinal study was based on 71 pregnant Finnish women, who donated blood samples in each trimester of pregnancy.

Results: Higher androgen concentrations were associated with an increased risk of overall EOC (e.g., testosterone ORT3 vs. T1: 1.56 [1.30-1.87], ptrend<0.0001), while the risk of endometrioid tumors increased with higher estradiol concentrations (ORT3 vs. T1: 2.76 [1.04-7.33], ptrend=0.03). Higher IGF-I was associated with a non-significant 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 inverse association between 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). No associations were observed between pre-diagnostic progesterone, SHBG, placental GH, and AMH with EOC risk overall, or by tumor invasiveness and histology.

The longitudinal study showed that hormone concentrations were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimesters. Further, 3rd trimester hormone concentrations can be estimated from 1st or 2nd trimester measurements.

Conclusion: Higher pre-diagnostic androgens, estradiol, and IGF-I are associated with EOC risk, and associations differ by tumor invasiveness and histology.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2015. 82 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1715
Keyword
epithelial ovarian cancer, sex steroid hormones, IGF-I, placental GH, AMH, pregnancy, prospective study
National Category
Medical Bioscience
Research subject
Pathology
Identifiers
urn:nbn:se:umu:diva-102181 (URN)978-91-7601-273-4 (ISBN)
Public defence
2015-05-22, Sal E04, By 6E, Norrlands Universitetssjukhus, Umeå universitet, Umeå, 09:00 (English)
Opponent
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Available from: 2015-04-29 Created: 2015-04-22 Last updated: 2015-05-08Bibliographically approved

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