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Association Between Sex Hormones and Colorectal Cancer Risk in Men and Women

  • Jennifer H. Lin
    Correspondence
    Reprint requests Address requests for reprints to: Jennifer H. Lin, PhD, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue East, Boston, Massachusetts 02215. fax: (617) 731-3843
    Affiliations
    Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • Shumin M. Zhang
    Affiliations
    Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • Kathryn M. Rexrode
    Affiliations
    Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • JoAnn E. Manson
    Affiliations
    Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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  • Andrew T. Chan
    Affiliations
    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

    Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts
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  • Kana Wu
    Affiliations
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
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  • Shelley S. Tworoger
    Affiliations
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • Susan E. Hankinson
    Affiliations
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

    Division of Biostatistics and Epidemiology, School of Public Health and Health Science, University of Massachusetts, Amherst, Massachusetts
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  • Charles Fuchs
    Affiliations
    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
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  • J. Michael Gaziano
    Affiliations
    Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

    Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

    Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, Massachusetts
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  • Julie E. Buring
    Affiliations
    Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
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  • Edward Giovannucci
    Affiliations
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

    Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
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Published:November 29, 2012DOI:https://doi.org/10.1016/j.cgh.2012.11.012

      Background & Aims

      There is observational and clinical evidence that indicates that sex hormones affect development of colorectal cancer in men and women. However, the relationship between endogenous sex hormone levels and colorectal cancer is unclear.

      Methods

      We collected data on lifestyle, medical history, and diet (through 2008), along with blood samples, from the Nurses' Health Study, the Women's Health Study, the Health Professional Follow-up Study, and the Physicians' Health Study II. We measured plasma levels of estrone, estradiol, testosterone, sex hormone binding globulin (SHBG), and C-peptide among 730 women (293 cases of colorectal cancer and 437 healthy individuals as controls) and 1158 men (439 colorectal cancer cases and 719 controls) and used unconditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals. All statistical tests were 2-sided.

      Results

      Total testosterone, SHBG, and the ratio of estradiol to testosterone were associated with colorectal cancer in men after adjustments for matching and risk factors for colorectal cancer, including body mass index and plasma levels of C-peptide. The RRs in the highest relative to the lowest quartile were 0.62 for testosterone (95% confidence interval, 0.40–0.96), 0.65 for SHBG (95% confidence interval, 0.42–0.99), and 2.63 for the ratio (95% confidence interval, 1.58–4.36) (P values for trend ≤ .02). However, in women, only the ratio of estradiol to testosterone was (inversely) associated with colorectal cancer after adjustments for all factors (RR, 0.43; 95% confidence interval, 0.22–0.84; P value for trend = .03).

      Conclusions

      On the basis of combined data from 4 population studies, there appears to be an association between levels of sex hormones and colorectal cancer risk in men. There also appears to be an inverse association between the ratio of estradiol to testosterone and colorectal cancer in postmenopausal women.

      Keywords

      Abbreviations used in this paper:

      BMI (body mass index), HPFS (Health Professional Follow-up Study), HT (hormone therapy), NHS (Nurses' Health Study), NYWHS (New York Women's Health Study), PHSII (Physicians' Health Study II), RRs (relative risks), SHBG (sex hormone binding globulin), WHS (Women's Health Study)
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