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

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; = 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; = 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.