umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Hormone concentrations during pregnancy and maternal risk of epithelial ovarian cancer
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
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 [en]
epithelial ovarian cancer, sex steroid hormones, IGF-I, placental GH, AMH, pregnancy, prospective study
National Category
Medical Bioscience
Research subject
Pathology
Identifiers
URN: urn:nbn:se:umu:diva-102181ISBN: 978-91-7601-273-4 (print)OAI: oai:DiVA.org:umu-102181DiVA: diva2:806991
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
List of papers
1. Anti-Mullerian hormone and risk of invasive serous ovarian cancer
Open this publication in new window or tab >>Anti-Mullerian hormone and risk of invasive serous ovarian cancer
Show others...
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
Keyword
Anti-Mullerian hormone, Ovarian neoplasms, Pregnancy, Case-control studies, Prospective studies
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-88941 (URN)10.1007/s10552-014-0363-9 (DOI)000334409500005 ()
Available from: 2014-05-22 Created: 2014-05-19 Last updated: 2017-12-05Bibliographically approved
2. Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer
Open this publication in new window or tab >>Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer
Show others...
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
Keyword
prospective study, case-control study, pregnancy, sex steroids, ovarian neoplasms
National Category
Medical Bioscience Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-98566 (URN)10.1530/ERC-14-0282 (DOI)000344788600007 ()25270324 (PubMedID)
Conference
EVELAND WS, 1996, STAT THEORY COMPUTAT, P10
Available from: 2015-01-28 Created: 2015-01-23 Last updated: 2017-12-05Bibliographically approved
3. Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study
Open this publication in new window or tab >>Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study
Show others...
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
Keyword
placental GH, IGF-I, ovarian neoplasms, pregnancy, prospective studies
National Category
Cancer and Oncology Medical Bioscience
Research subject
Pathology
Identifiers
urn:nbn:se:umu:diva-102011 (URN)10.1002/ijc.29387 (DOI)000354287600018 ()25516257 (PubMedID)
Note

Article first published online: 17 DEC 2014

Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2017-12-04Bibliographically approved
4. Longitudinal Assessment of Pregnancy Hormones
Open this publication in new window or tab >>Longitudinal Assessment of Pregnancy Hormones
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood. We used serial serum samples from 71 pregnant women (25 primiparous, 25 biparous, and 21 with 2 consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester. Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g. estradiol, 1st vs. 2nd and 2nd vs. 3rd trimester r=0.51 and r=0.60, p<0.01; 1st vs. 3rd trimester r=0.32, p<0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R²T1=16% and R²T2=42%). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones. In conclusion, one hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations.

Keyword
Longitudinal study, pregnancy, steroid hormones, OPG, sRANKL
National Category
Medical Bioscience Obstetrics, Gynecology and Reproductive Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:umu:diva-102003 (URN)
Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2015-04-27Bibliographically approved

Open Access in DiVA

Hormone Concentrations during Pregnancy and Maternal Risk kof Epithelial Ovarian Cancer(726 kB)1308 downloads
File information
File name FULLTEXT01.pdfFile size 726 kBChecksum SHA-512
aac421f1dc8ea63e5bb8e4460dd3952afef5604050b4788117474ffc15be057d85a62587cff9ef4b818ae9d9dfec20d861c74e952f486e63505f9c07899685ea
Type fulltextMimetype application/pdf
Spikblad(26 kB)10 downloads
File information
File name SPIKBLAD01.pdfFile size 26 kBChecksum SHA-512
4d7ad8e01f0a3e500240b82db82133c8d2f26e00de224958766f0479563cfad63a764408e1799e28753889063bece28f8099c3967f13a5333303876438a53c92
Type spikbladMimetype application/pdf

Authority records BETA

Schock, Helena

Search in DiVA

By author/editor
Schock, Helena
By organisation
Department of Medical Biosciences
Medical Bioscience

Search outside of DiVA

GoogleGoogle Scholar
Total: 1308 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1264 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf