title: Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer.
abstract: BACKGROUND
  It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.
  
  
  METHODS
  We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.
  
  
  RESULTS
  Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.
  
  
  CONCLUSIONS
  Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA. anne.jacquotte@nyumc.org
authors.forename: A
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
authors.forename: R E
authors.initials: RE
authors.lastname: Shore
authors.forename: Y
authors.initials: Y
authors.lastname: Afanasyeva
authors.forename: A
authors.initials: A
authors.lastname: Lukanova
authors.forename: S
authors.initials: S
authors.lastname: Sieri
authors.forename: K L
authors.initials: KL
authors.lastname: Koenig
authors.forename: A
authors.initials: A
authors.lastname: Idahl
authors.forename: V
authors.initials: V
authors.lastname: Krogh
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Ohlson
authors.forename: P
authors.initials: P
authors.lastname: Muti
authors.forename: A A
authors.initials: AA
authors.lastname: Arslan
authors.forename: P
authors.initials: P
authors.lastname: Lenner
authors.forename: F
authors.initials: F
authors.lastname: Berrino
authors.forename: G
authors.initials: G
authors.lastname: Hallmans
authors.forename: P
authors.initials: P
authors.lastname: Toniolo
authors.forename: E
authors.initials: E
authors.lastname: Lundin
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000453:epidemiology*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D004967:Estrogens; D006894:Hydroxyestrones; C026702:16-hydroxyestrone; C024980:2-hydroxyestrone