title: A Prospective Evaluation of Endogenous Sex Hormone Levels and Colorectal Cancer Risk in Postmenopausal Women.
abstract: BACKGROUND
  Postmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain.
  
  
  METHODS
  The relation of colorectal cancer risk with circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone and sex hormone-binding globulin (SHBG) was determined in a nested case-control study of 1203 postmenopausal women (401 case patients and 802 age and race/ethnicity-matched control patients) enrolled in the Women's Health Initiative Clinical Trial (WHI-CT) who were not assigned to the estrogen-alone or combined estrogen plus progestin intervention groups. We used multivariable-adjusted conditional logistic regression models that included established colorectal cancer risk factors. All statistical tests were two-sided.
  
  
  RESULTS
  Comparing extreme quartiles, estrone (odds ratio [OR]q4-q1 = 0.44, 95% confidence interval [CI] = 0.28 to 0.68, P trend = .001), free estradiol (ORq4-q1 = 0.43, 95% CI = 0.27 to 0.69, P trend ≤ .0001), and total estradiol (ORq4-q1 = 0.58, 95% CI = 0.38 to 0.90, P trend = .08) were inversely associated with colorectal cancer risk. SHBG levels were positively associated with colorectal cancer development (OR[q4-q1] = 2.30, 95% CI = 1.51 to 3.51, P trend ≤ .0001); this association strengthened after further adjustment for estradiol and estrone (ORq4-q1 = 2.50, 95% CI = 1.59 to 3.92, P trend < .0001). Progesterone was not associated with colorectal cancer risk.
  
  
  CONCLUSIONS
  Endogenous estrogen levels were inversely, and SHBG levels positively, associated with colorectal cancer risk, even after control for several colorectal cancer risk factors. These results suggest that endogenous estrogens may confer protection against colorectal tumorigenesis among postmenopausal women.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP). neil.murphy@imperial.ac.uk.
authors.forename: Neil
authors.initials: N
authors.lastname: Murphy
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: Gloria Y F
authors.initials: GY
authors.lastname: Ho
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK (NM, MJG); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY (HDS, XX, SWS, TER, GYFH); Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, Los Angeles, CA (FZS); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, JDP); Centre for Public Health Research, Massey University, Wellington, New Zealand (JDP).
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000453:epidemiology*; D015986:Confounding Factors, Epidemiologic; D004958:Estradiol / Q000097:blood*; D004970:Estrone / Q000097:blood*; D005215:Fasting; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D018579:Patient Selection; D017698:Postmenopause / Q000097:blood*; D011374:Progesterone / Q000097:blood*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D014481:United States / Q000453:epidemiology
chemical_list: D007328:Insulin; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein