title: Circulating Estrogens and Postmenopausal Ovarian Cancer Risk in the Women's Health Initiative Observational Study.
abstract: Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS).
  
  
  
  We selected all 169 eligible epithelial ovarian cancer cases and 412 matched controls from women enrolled in WHI-OS who were not using menopausal hormones at baseline. Baseline levels of 15 estrogens and estrogen metabolites were measured via liquid chromatography/tandem mass spectrometry. Associations with ovarian cancer risk overall and stratified by histologic subtype (serous/nonserous) were analyzed using logistic regression. The mean time from serum collection to cancer diagnosis was 6.9 years.
  
  
  
  Overall, we observed modest ovarian cancer risk associations among women with higher levels of estrone [OR (95% confidence interval) quintile (Q)5 vs. Q1: 1.54 (0.82-2.90), Ptrend = 0.05], as well as 2- and 4-methoxyestrone metabolites [2.03 (1.06-3.88), Ptrend = 0.02; 1.86 (0.98-3.56), Ptrend = 0.01, respectively]. Associations of estrogens and estrogen metabolites varied substantially by histologic subtype. Associations with serous tumors were universally null, while estrone [2.65 (1.09-6.45), Ptrend = 0.01, Pheterogeneity = 0.04], unconjugated estradiol [2.72 (1.04-7.14), Ptrend = 0.03, Pheterogeneity = 0.02] and many of the 2-, 4-, and 16-pathway metabolites were positively associated with nonserous tumors.
  
  
  
  Our study provides novel molecular data showing an association of the parent estrogens and several estrogen metabolites with nonserous ovarian cancers.
  
  
  
  These findings further support the heterogeneous etiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 648-56. ©2016 AACR.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. britton.trabert@nih.gov.
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.affiliation: Department of Hematology and Medical Oncology, University of Texas at San Antonio, San Antonio, Texas.
authors.forename: Sarunas
authors.initials: S
authors.lastname: Sliesoraitis
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.affiliation: Women's Health Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Margery L
authors.initials: ML
authors.lastname: Gass
authors.affiliation: Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Fuhrman
authors.affiliation: Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004967:Estrogens / Q000097:blood*; D005260:Female; D014943:Global Health; D006801:Humans; D008875:Middle Aged; D064887:Observational Studies as Topic; D010051:Ovarian Neoplasms / Q000097:blood / Q000209:etiology*; D017698:Postmenopause / Q000097:blood*; D012307:Risk Factors; D016387:Women's Health
chemical_list: D004967:Estrogens