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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Estrogen Receptor-β Expression of Ovarian Tumors and Its Association with Ovarian Cancer Risk Factors

Amy L. Shafrir, Ana Babic, Margaret Gates Kuliszewski, Megan S. Rice, Mary K. Townsend, Jonathan L. Hecht and Shelley S. Tworoger
Amy L. Shafrir
1Division of Adolescent/Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
2Boston Center for Endometriosis, Brigham and Women's Hospital and Boston Children's Hospital, Boston, Massachusetts.
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  • For correspondence: amy.shafrir@childrens.harvard.edu
Ana Babic
3Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
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Margaret Gates Kuliszewski
4Department of Epidemiology and Biostatistics, University of Albany SUNY School of Public Health, Albany, New York.
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  • ORCID record for Margaret Gates Kuliszewski
Megan S. Rice
5Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
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Mary K. Townsend
6Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
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Jonathan L. Hecht
7Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
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Shelley S. Tworoger
6Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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DOI: 10.1158/1055-9965.EPI-20-0618 Published November 2020
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Abstract

Background: Differential associations between ovarian cancer risk factors and estrogen receptor-α (ERα) ovarian tumor expression have been noted; however, no research has assessed estrogen receptor-β (ERβ) expression. Thus, in exploratory analyses, we assessed the association of several factors with ovarian cancer risk by ERβ tumor status.

Methods: We conducted a nested case–control study within the prospective Nurses' Health Study cohorts (NHS/NHSII), with exposures collected through biennial questionnaires. Paraffin-embedded tumor blocks were requested for cases diagnosed from 1976 to 2006 (NHS) and 1989 to 2005 (NHSII) and tissue microarrays were stained for nuclear ERβ (ERβ-nuc) and cytoplasmic ERβ (ERβ-cyto), with any staining considered positive (+). We obtained odds ratios (OR) and 95% confidence intervals (CI) using multivariate polytomous logistic regression.

Results: We included 245 cases [43% ERβ-cyto (+) and 71% ERβ-nuc (+)] and 1,050 matched controls. An inverse association was observed between parity and risk of ERβ-nuc (+) (OR, parous vs. nulliparous: 0.46; 95% CI, 0.26–0.81), but not ERβ-nuc (–) tumors (OR, parous vs. nulliparous: 1.51; 95% CI, 0.45–5.04; Pheterogeneity = 0.04). Conversely, parity was inversely associated with ERβ-cyto (–) tumors (OR, parous vs. nulliparous: 0.42; 95% CI, 0.23–0.78), but was not associated with ERβ-cyto (+) tumors (OR, parous vs. nulliparous: 1.08; 95% CI, 0.45–2.63; Pheterogeneity = 0.05). Associations for other exposures, including hormone therapy, did not differ by ERβ-nuc or ERβ-cyto status.

Conclusions: Our results suggest that parity may influence ovarian cancer risk, in part, through alterations in ERβ localization within tumor cells.

Impact: Alterations in ERβ expression and localization appear to be important for ovarian cancer etiology. Future research should confirm our results and assess potential biologic mechanisms for the observed associations.

This article is featured in Highlights of This Issue, p. 2105

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Cancer Epidemiol Biomarkers Prev 2020;29:2211–9

  • Received April 27, 2020.
  • Revision received June 16, 2020.
  • Accepted August 4, 2020.
  • Published first August 20, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 29 (11)
November 2020
Volume 29, Issue 11
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Estrogen Receptor-β Expression of Ovarian Tumors and Its Association with Ovarian Cancer Risk Factors
Amy L. Shafrir, Ana Babic, Margaret Gates Kuliszewski, Megan S. Rice, Mary K. Townsend, Jonathan L. Hecht and Shelley S. Tworoger
Cancer Epidemiol Biomarkers Prev November 1 2020 (29) (11) 2211-2219; DOI: 10.1158/1055-9965.EPI-20-0618

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Estrogen Receptor-β Expression of Ovarian Tumors and Its Association with Ovarian Cancer Risk Factors
Amy L. Shafrir, Ana Babic, Margaret Gates Kuliszewski, Megan S. Rice, Mary K. Townsend, Jonathan L. Hecht and Shelley S. Tworoger
Cancer Epidemiol Biomarkers Prev November 1 2020 (29) (11) 2211-2219; DOI: 10.1158/1055-9965.EPI-20-0618
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