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Circulating androgens and postmenopausal ovarian cancer risk in the Women's Health Initiative Observational Study

  1. Author:
    Trabert, Britton [ORCID]
    Michels, Kara A
    Anderson, Garnet L
    Brinton, Louise A
    Falk, Roni T [ORCID]
    Geczik, Ashley M
    Harris, Holly R
    Pan, Kathy
    Pfeiffer, Ruth M
    Qi, Lihong
    Rohan, Thomas
    Wentzensen, Nicolas
    Xu,Xia

  2. Author Address

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland., Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington., Division of Public Health Sciences, Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington., Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California., Public Health Sciences, School of Medicine, UC Davis, Sacramento, California., Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York; Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania., Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.,
    1. Year: 2019
    2. Date: Oct 15
    3. Epub Date: 2019 01 26
  2. Journal: International journal of cancer
    1. 145
    2. 8
    3. Pages: 2051-2060
  4. Type of Article: Article
  5. ISSN: 0020-7136
  1. Abstract:

    Our knowledge of epidemiologic risk factors for ovarian cancer supports a role for androgens in the pathogenesis of this disease; however, few studies have examined associations between circulating androgens and ovarian cancer risk. Using highly sensitive LC-MS/MS assays, we evaluated associations between pre-diagnostic serum levels of 12 androgens, including novel androgen metabolites that reflect androgen activity in tissues, and ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). We frequency-matched 169 ovarian cancer cases to 410 controls from women enrolled in WHI-OS who were not using menopausal hormones at enrollment/blood draw. We estimated associations overall and by subtype (n=102 serous/67 non-serous) using multivariable adjusted logistic regression. Androgen/androgen metabolite levels were not associated with overall ovarian cancer risk. In analyses by subtype, women with increased levels of androsterone-glucuronide (ADT-G) and total 5-a reduced glucuronide metabolites (markers of tissue-level androgenic activity) were at increased risk of developing non-serous ovarian cancer: ADT-G tertile (T)3 versus T1 odds ratio [OR] (95% confidence interval [CI]) 4.36 (1.68-11.32), p-heterogeneity 0.002; total glucuronide metabolites 3.63 (1.47-8.95), 0.002. Risk of developing serous tumors was unrelated to these markers. ADT-G and total glucuronide metabolites, better markers of tissue-level androgenic activity in women than testosterone, were associated with an increased risk of developing non-serous ovarian cancer. Our work demonstrates that sex steroid metabolism is important in the etiology of non-serous ovarian cancers and supports a heterogeneous hormonal etiology across histologic subtypes of ovarian cancer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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External Sources

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  2. DOI: 10.1002/ijc.32157
  3. PMID: 30684389
  4. View record in Web of Science®
  5. WOS: 000482098200004

Library Notes

  1. Fiscal Year: FY2018-2019
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