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

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-α 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.

• Authors: Britton Trabert, Kara A Michels, Garnet L Anderson, Louise A Brinton, Roni T Falk, Ashley M Geczik, Holly R Harris, Kathy Pan, Ruth M Pfeiffer, Lihong Qi, Thomas Rohan, Nicolas Wentzensen, Xia Xu
• Journal: International journal of cancer (Int J Cancer) Vol. 145 Issue 8 Pg. 2051-2060 (10 15 2019) ISSN: 1097-0215 [Electronic] United States
• PMID: 30684389 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: © 2019 UICC.

Chemical References

• Androgens
• Glucuronides
• androsterone glucuronide
• Androsterone

Topics

• Aged
• Androgens (blood)
• Androsterone (analogs & derivatives, blood)
• Case-Control Studies
• Chromatography, Liquid
• Female
• Glucuronides (blood, metabolism)
• Humans
• Logistic Models
• Middle Aged
• Ovarian Neoplasms (blood, diagnosis)
• Postmenopause (blood)
• Risk Factors
• Tandem Mass Spectrometry
• Women's Health