title: The ratio of the estradiol metabolites 2-hydroxyestrone (2-OHE1) and 16α-hydroxyestrone (16-OHE1) may predict breast cancer risk in postmenopausal but not in premenopausal women: two case-control studies.
abstract: OBJECTIVE
  Two main estradiol metabolites have different biological behavior with tumorigenic features of 16-OHE1 and antiproliferative characteristics of 2-OHE1. We investigated the ratio of these estradiol metabolites in pre- and postmenopausal patients with breast cancer (BC) within two case-control studies.
  
  
  METHODS
  From 41 premenopausal patients with (cases) and without (controls N = 211) BC and 207 postmenopausal patients with and without BC (N = 206), urine samples were collected. Urine samples were collected prior to surgery and stored at -20 °C until measurement by ELISA. The multiple linear regression test with two interactions was performed to evaluate the influence of different factors on the metabolic ratio.
  
  
  RESULTS
  In premenopausal patients, log ratio of 2-OHE1/16-OHE1 was 0.25 (CI 0.20;0.29) and 0.21 (CI 0.11;0.31) for controls and cases without significant difference. In postmenopausal patients, log ratio was 0.22 (CI 0.17;0.26) and 0.11 (CI 0.07;0.15) in controls and cases, respectively, and was statistically significantly lower (p = 0.0002). Log ratio was significantly influenced by BMI, but only in postmenopausal patients, an increased BMI resulted in a significantly (p < 0.042) decreased ratio.
  
  
  CONCLUSIONS
  Our case control studies suggest that in postmenopausal women a different metabolism of estrogens may play a role in the tumorigenesis of breast cancer. This genetically determined metabolism could be influenced by the exogenic factor BMI. In premenopausal women different hormone levels at different time points of the menstrual cycle may be an explanation that why we could not find an influence of estrogen metabolism.
authors.affiliation: Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Ruan
authors.forename: Harald
authors.initials: H
authors.lastname: Seeger
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Alfred O
authors.initials: AO
authors.lastname: Mueck
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D001943:Breast Neoplasms / Q000235:genetics / Q000652:urine*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004958:Estradiol / Q000378:metabolism / Q000652:urine*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006894:Hydroxyestrones / Q000652:urine*; D008875:Middle Aged; D017698:Postmenopause / Q000652:urine; D017697:Premenopause / Q000652:urine; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D004967:Estrogens; D006894:Hydroxyestrones; C026702:16-hydroxyestrone; D004958:Estradiol; C024980:2-hydroxyestrone