title: Estrogen Metabolites Are Not Associated with Colorectal Cancer Risk in Postmenopausal Women.
abstract: BACKGROUND
  A potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women.
  
  
  METHODS
  We followed 15,595 women (ages 55-80 years) enrolled in the Breast and Bone Follow-up to the Fracture Intervention Trial (B∼FIT) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 colorectal cancer cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position) and by ratios of the groupings using Cox proportional hazards regression models.
  
  
  RESULTS
  No significant associations were seen for estrone (HRQ4 vs. Q1 = 1.15; 95% CI, 0.69-1.93; Ptrend = 0.54), estradiol (HRQ4 vs. Q1 = 0.98; 95% CI, 0.58-1.64; Ptrend > 0.99), or total EM (the sum of all EM; HRQ4 vs. Q1 = 1.35; 95% CI, 0.81-2.24; Ptrend = 0.33). Most metabolites in the 2-, 4-, or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol.
  
  
  CONCLUSIONS
  Circulating estrogens and their metabolites were generally unrelated to colorectal cancer risk in postmenopausal women.
  
  
  CONCLUSIONS
  Additional studies are needed to understand how exogenous estrogen may prevent colorectal cancer.
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. falkr@mail.nih.gov.
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Department of Epidemiology and Biostatistics, University of Maryland School of Public Health, College Park, Maryland.
authors.forename: Cher M
authors.initials: CM
authors.lastname: Dallal
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, California.
authors.forename: James V
authors.initials: JV
authors.lastname: Lacey
authors.affiliation: Department of Medicine, University of California, San Francisco, California.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Bauer
authors.affiliation: Group Health Research Institute, Seattle, Washington.
authors.forename: Diana S M
authors.initials: DS
authors.lastname: Buist
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Trisha F
authors.initials: TF
authors.lastname: Hue
authors.affiliation: Division of Epidemiology, University of California San Diego, La Jolla, California.
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.affiliation: Department of Medicine, University of California, San Francisco, California.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Tice
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, Leidos-Frederick (formerly SAIC-Frederick), Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: C2N Diagnostics, St. Louis, Missouri.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000453:epidemiology*; D004958:Estradiol / Q000097:blood*; D004964:Estriol / Q000097:blood; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000097:blood*; D005260:Female; D006801:Humans; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D012307:Risk Factors
chemical_list: D004967:Estrogens; D004970:Estrone; D004958:Estradiol; D004964:Estriol