title: Serum Estrogens and Estrogen Metabolites and Endometrial Cancer Risk among Postmenopausal Women.
abstract: Although endometrial cancer is clearly influenced by hormonal factors, few epidemiologic studies have investigated the role of endogenous estrogens or especially estrogen metabolites.
  
  
  
  We conducted a nested case-control study within the Women's Health Initiative Observational Study (WHI-OS), a cohort of 93,676 postmenopausal women recruited between 1993 and 1998. Using baseline serum samples from women who were non-current hormone users with intact uteri, we measured 15 estrogens/estrogen metabolites via HPLC/MS-MS among 313 incident endometrial cancer cases (271 type I, 42 type II) and 354 matched controls, deriving adjusted ORs and 95% confidence intervals (CI) for overall and subtype-specific endometrial cancer risk.
  
  
  
  Parent estrogens (estrone and estradiol) were positively related to endometrial cancer risk, with the highest risk observed for unconjugated estradiol (OR 5th vs. 1st quintile = 6.19; 95% CI, 2.95-13.03, Ptrend = 0.0001). Nearly all metabolites were significantly associated with elevated risks, with some attenuation after adjustment for unconjugated estradiol (residual risks of 2- to 3-fold). Body mass index (kg/m(2), BMI) relations were somewhat reduced after adjustment for estrogen levels. The association with unconjugated estradiol was stronger for type I than type II tumors (Phet = 0.01).
  
  
  
  Parent estrogens as well as individual metabolites appeared to exert generalized uterotropic activity, particularly for type I tumors. The effects of obesity on risk were only partially explained by estrogens.
  
  
  
  These findings enhance our understanding of estrogen mechanisms involved in endometrial carcinogenesis but also highlight the need for studying additional markers that may underlie the effects on risk of certain risk factors, for example, obesity. Cancer Epidemiol Biomarkers Prev; 25(7); 1081-9. ©2016 AACR.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. brintonl@exchange.nih.gov.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
authors.affiliation: Division of Public Health Sciences, 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: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. Division of Epidemiology, The Ohio State University College of Public Health, Columbus, Ohio.
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Felix
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: Cleveland, Ohio.
authors.forename: Margery L
authors.initials: ML
authors.lastname: Gass
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
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: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
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: 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; D014408:Biomarkers, Tumor / Q000097:blood*; D063646:Carcinogenesis; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000097:blood* / Q000453:epidemiology; D004958:Estradiol / Q000097:blood* / Q000378:metabolism; D004970:Estrone / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause / Q000097:blood*; D012307:Risk Factors; D057566:Self Report; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D004970:Estrone; D004958:Estradiol