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Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Oulu, Finland.
Umeå University, Faculty of Medicine, Department of Biobank Research. New York, USA.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
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2014 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 6, 831-844 p.Article in journal (Refereed) Published
Abstract [en]

Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E-2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E-2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.

Place, publisher, year, edition, pages
Society for Endocrinology , 2014. Vol. 21, no 6, 831-844 p.
Keyword [en]
prospective study, case-control study, pregnancy, sex steroids, ovarian neoplasms
National Category
Medical Bioscience Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-98566DOI: 10.1530/ERC-14-0282ISI: 000344788600007PubMedID: 25270324OAI: oai:DiVA.org:umu-98566DiVA: diva2:784128
Conference
EVELAND WS, 1996, STAT THEORY COMPUTAT, P10
Available from: 2015-01-28 Created: 2015-01-23 Last updated: 2017-12-05Bibliographically 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
Supervisors
Available from: 2015-04-29 Created: 2015-04-22 Last updated: 2015-05-08Bibliographically approved

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Schock, HelenaGrankvist, KjellLakso, Hans-ÅkeLundin, Eva

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