Estrogen Receptor-β Expression of Ovarian Tumors and Its Association with Ovarian Cancer Risk Factors.

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; P heterogeneity = 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; P heterogeneity = 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.

• Authors: Amy L Shafrir, Ana Babic, Margaret Gates Kuliszewski, Megan S Rice, Mary K Townsend, Jonathan L Hecht, Shelley S Tworoger
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 29 Issue 11 Pg. 2211-2219 (11 2020) ISSN: 1538-7755 [Electronic] United States
• PMID: 32856599 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Estrogen Receptor beta

Topics

• Adult
• Case-Control Studies
• Estrogen Receptor beta (metabolism)
• Female
• Humans
• Middle Aged
• Ovarian Neoplasms (blood, pathology)
• Prospective Studies
• Risk Factors