PMID- 32856599 OWN - NLM STAT- MEDLINE DCOM- 20211221 LR - 20211221 IS - 1538-7755 (Electronic) IS - 1055-9965 (Print) IS - 1055-9965 (Linking) VI - 29 IP - 11 DP - 2020 Nov TI - Estrogen Receptor-beta Expression of Ovarian Tumors and Its Association with Ovarian Cancer Risk Factors. PG - 2211-2219 LID - 10.1158/1055-9965.EPI-20-0618 [doi] AB - BACKGROUND: Differential associations between ovarian cancer risk factors and estrogen receptor-alpha (ERalpha) ovarian tumor expression have been noted; however, no research has assessed estrogen receptor-beta (ERbeta) expression. Thus, in exploratory analyses, we assessed the association of several factors with ovarian cancer risk by ERbeta 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 ERbeta (ERbeta-nuc) and cytoplasmic ERbeta (ERbeta-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% ERbeta-cyto (+) and 71% ERbeta-nuc (+)] and 1,050 matched controls. An inverse association was observed between parity and risk of ERbeta-nuc (+) (OR, parous vs. nulliparous: 0.46; 95% CI, 0.26-0.81), but not ERbeta-nuc (-) tumors (OR, parous vs. nulliparous: 1.51; 95% CI, 0.45-5.04; P (heterogeneity) = 0.04). Conversely, parity was inversely associated with ERbeta-cyto (-) tumors (OR, parous vs. nulliparous: 0.42; 95% CI, 0.23-0.78), but was not associated with ERbeta-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 ERbeta-nuc or ERbeta-cyto status. CONCLUSIONS: Our results suggest that parity may influence ovarian cancer risk, in part, through alterations in ERbeta localization within tumor cells. IMPACT: Alterations in ERbeta 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. CI - (c)2020 American Association for Cancer Research. FAU - Shafrir, Amy L AU - Shafrir AL AD - Division of Adolescent/Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts. amy.shafrir@childrens.harvard.edu. AD - Boston Center for Endometriosis, Brigham and Women's Hospital and Boston Children's Hospital, Boston, Massachusetts. FAU - Babic, Ana AU - Babic A AD - Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. FAU - Gates Kuliszewski, Margaret AU - Gates Kuliszewski M AUID- ORCID: 0000-0002-2111-6227 AD - Department of Epidemiology and Biostatistics, University of Albany SUNY School of Public Health, Albany, New York. FAU - Rice, Megan S AU - Rice MS AD - Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Townsend, Mary K AU - Townsend MK AUID- ORCID: 0000-0003-2452-4477 AD - Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. FAU - Hecht, Jonathan L AU - Hecht JL AUID- ORCID: 0000-0003-4771-2585 AD - Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts. FAU - Tworoger, Shelley S AU - Tworoger SS AUID- ORCID: 0000-0002-6986-7046 AD - Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. LA - eng GR - P01 CA087969/CA/NCI NIH HHS/United States GR - U01 CA176726/CA/NCI NIH HHS/United States GR - P50 CA105009/CA/NCI NIH HHS/United States GR - UM1 CA186107/CA/NCI NIH HHS/United States GR - R01 CA054419/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20200820 PL - United States TA - Cancer Epidemiol Biomarkers Prev JT - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JID - 9200608 RN - 0 (Estrogen Receptor beta) SB - IM MH - Adult MH - Case-Control Studies MH - Estrogen Receptor beta/*metabolism MH - Female MH - Humans MH - Middle Aged MH - Ovarian Neoplasms/*blood/pathology MH - Prospective Studies MH - Risk Factors PMC - PMC7641961 MID - NIHMS1619716 COIS- Conflict of interest: A.L. Shafrir reports grants from the NIH and the Marriott Family Foundations, outside the submitted work. M.S. Rice reports employment with Sanofi, all work in this article was completed prior to her employment at Sanofi. J.L. Hecht reports grants from NIH/NCI (2P01CA87969, principal investigator: Meir Stampfer) during the conduct of the study. S.S. Tworoger reports grants from NCI during the conduct of the study. No potential conflicts of interest were disclosed by the other authors. EDAT- 2020/08/29 06:00 MHDA- 2021/12/22 06:00 PMCR- 2021/05/01 CRDT- 2020/08/29 06:00 PHST- 2020/04/27 00:00 [received] PHST- 2020/06/16 00:00 [revised] PHST- 2020/08/04 00:00 [accepted] PHST- 2020/08/29 06:00 [pubmed] PHST- 2021/12/22 06:00 [medline] PHST- 2020/08/29 06:00 [entrez] PHST- 2021/05/01 00:00 [pmc-release] AID - 1055-9965.EPI-20-0618 [pii] AID - 10.1158/1055-9965.EPI-20-0618 [doi] PST - ppublish SO - Cancer Epidemiol Biomarkers Prev. 2020 Nov;29(11):2211-2219. doi: 10.1158/1055-9965.EPI-20-0618. Epub 2020 Aug 20.