title: Profiling of endogenous estrogens, their precursors, and metabolites in endometrial cancer patients: association with risk and relationship to clinical characteristics.
abstract: BACKGROUND
  Endometrial cancer (EC) predominantly occurs after menopause and is strongly related to steroid hormones, particularly estrogens. However, the relationship between these hormones and clinical characteristics remains unaddressed.
  
  
  METHODS
  We analyzed the circulating levels of 18 steroids including adrenal precursors, androgens, estrogens, and their glucuronide metabolites, using specific and validated methods based on tandem mass spectrometry. Our goals were to compare circulating levels in postmenopausal women with EC (n = 126) with those of healthy postmenopausal women (n = 110) and to investigate how these hormonal levels relate to clinical characteristics.
  
  
  RESULTS
  After adjustment for potential confounders, most hormones were significantly elevated in EC patients compared with healthy controls. In women with type I cancer, estrogen levels were up to 3-fold those of healthy women (P < 0.05). These higher levels were associated with an increased risk of cancer, particularly estrogens and their direct precursors, testosterone and androstenedione (odds ratios ranging from 4.4 to 13.3; P ≤ 0.0003). Elevated circulating levels of estrogens and their metabolites were found in cancer cases with type I endometrioid cancer and low-grade and noninvasive tumor, suggesting an association between these hormones and the tumoral estrogenic activity. In addition, levels of estrone-sulfate in EC patients with relapse were 2-fold over levels of EC patients without relapse (P < 0.05), and 4.5-fold over those of healthy women (P < 0.001).
  
  
  CONCLUSIONS
  Circulating levels of steroids were associated with increased risk of EC. Estrogens may represent novel biomarkers predictive of clinical characteristics, including evidence for an increased risk of relapse.
authors.affiliation: Centre Hospitalier Universitaire de Québec Research Center, Laval Universiy, Québec, Canada.
authors.forename: Etienne
authors.initials: E
authors.lastname: Audet-Walsh
authors.forename: Johanie
authors.initials: J
authors.lastname: Lépine
authors.forename: Jean
authors.initials: J
authors.lastname: Grégoire
authors.forename: Marie
authors.initials: M
authors.lastname: Plante
authors.forename: Patrick
authors.initials: P
authors.lastname: Caron
authors.forename: Bernard
authors.initials: B
authors.lastname: Têtu
authors.forename: Pierre
authors.initials: P
authors.lastname: Ayotte
authors.forename: Jacques
authors.initials: J
authors.lastname: Brisson
authors.forename: Lyne
authors.initials: L
authors.lastname: Villeneuve
authors.forename: Alain
authors.initials: A
authors.lastname: Bélanger
authors.forename: Chantal
authors.initials: C
authors.lastname: Guillemette
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000097:blood / Q000378:metabolism*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009215:Myometrium / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D011247:Pregnancy; D012306:Risk; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D012907:Smoking / Q000378:metabolism; D013256:Steroids / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D003278:Contraceptives, Oral, Hormonal; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D013256:Steroids