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Anti-Mullerian hormone and risk of invasive serous ovarian cancer
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Oulu, Finland.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
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2014 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, no 5, 583-589 p.Article in journal (Refereed) Published
Abstract [en]

Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer. A case-control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986-2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations. Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49-1.77 for top vs. bottom tertile, P (trend) = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06-2.54) was observed in younger women, P (homogeneity) = 0.002. In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.

Place, publisher, year, edition, pages
Springer, 2014. Vol. 25, no 5, 583-589 p.
Keyword [en]
Anti-Mullerian hormone, Ovarian neoplasms, Pregnancy, Case-control studies, Prospective studies
National Category
Cancer and Oncology
URN: urn:nbn:se:umu:diva-88941DOI: 10.1007/s10552-014-0363-9ISI: 000334409500005OAI: diva2:718985
Available from: 2014-05-22 Created: 2014-05-19 Last updated: 2016-02-18Bibliographically 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.
Umeå University medical dissertations, ISSN 0346-6612 ; 1715
epithelial ovarian cancer, sex steroid hormones, IGF-I, placental GH, AMH, pregnancy, prospective study
National Category
Medical Bioscience
Research subject
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)
Available from: 2015-04-29 Created: 2015-04-22 Last updated: 2015-05-08Bibliographically approved

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