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Case–control study of endogenous sex steroid hormones and risk of endometrial cancer

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Abstract

Background

Epidemiologic evidence regarding the role of endogenous sex hormones in endometrial cancer etiology remains inconsistent. The objective of this study was to investigate if circulating levels of endogenous estrone, estradiol, sex hormone binding globulin (SHBG), testosterone, and androstenedione are associated with endometrial cancer risk.

Methods

We conducted a population-based case–control study of 522 incident endometrial cancer cases and 976 population controls, in Alberta, Canada from 2002 to 2006. Study participants completed in-person interviews and provided fasting blood samples. Sex hormone levels were determined by enzyme-linked immunosorbent assays.

Results

Higher levels of androstenedione were associated with increased endometrial cancer risk (OR 1.44, 95% CI 1.04–2.02). Endometrial cancer risk in pre- and peri-menopausal women was reduced for the highest versus lowest quartiles of estrone (OR 0.44, 95% CI 0.22–0.88) and estradiol (OR 0.30, 95% CI 0.14–0.65), but in post-menopausal women, the endometrial cancer risk was increased for the highest versus lowest quartile of androstenedione (OR 1.82, 95% CI 1.25–2.65). In addition, endometrial cancer risk in normal/underweight women was decreased for the highest versus lowest quartile of serum SHBG (OR 0.39, 95% CI 0.19–0.84).

Conclusions

Overall, positive associations were found for androstenedione concentrations, while sub-group analyses revealed = inverse associations with estrogens and SHBG. Results of this study provide empirical evidence for the role of circulating sex hormones in endometrial cancer etiology and highlight the importance of modifiable factors that contribute to changes in sex hormone concentration levels.

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Acknowledgments

Study coordination was done by Rita Biel, Lisa Strosher, Pam Round, and Aleata Rhyorchuk. Laboratory assays were conducted by Angela Dang-Krawetz in the laboratory of Dr David C.W. Lau at the University of Calgary. Colleen Lachance, Maryann Lester, Lisa Miller, Catherine Munro, and Polly Pratt recruited controls. Participant interviews were conducted by Tamara Bellmont, Kay Christie, Pearl Cooke, Linda Davison, Carolyn Henderson, Tacey Lawrence, Rosalie Merkosky, Jodi Parrotta, Brenda Platzer, Cyndi Rasa, Nicole Slot, Keely Winnitoy, and Carol-Anne Zawalykut. Quality control of interviews was performed by Jodi Parrotta. Carla Quesnel assisted with administrative tasks and Holly Wilson identified cases from Calgary Laboratory Service pathology reports. Farit Vakhetov did data management and Qinggang Wang assisted with final verification of statistical analyses.

Funding

This study was funded by research grants from the National Cancer Institute of Canada with funds from the Canadian Cancer Society. C.M. Friedenreich received career awards from the Canadian Institutes of Health Research, the Alberta Heritage Foundation for Medical Research (AHFMR), Alberta Innovates-Health Solutions, and from the Alberta Cancer Foundation Weekend to End Women’s Cancers Breast Cancer Chair. L.S. Cook and K.S. Courneya held Canada Research Chairs and L.S. Cook also received career award funding from AHFMR and support from UNM Cancer Center P30CA118100.

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Authors and Affiliations

  1. Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, AB, Canada

    Christine M. Friedenreich, Thomas Speidel, Darren R. Brenner & Emily Heer

  2. Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Christine M. Friedenreich & Darren R. Brenner

  3. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Christine M. Friedenreich, Darren R. Brenner & Linda S. Cook

  4. Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands

    Jeroen W. G. Derksen

  5. Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Jeroen W. G. Derksen

  6. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Jeroen W. G. Derksen

  7. Faculty of Kinesiology, Sport and Recreation, University of Alberta, Edmonton, AB, Canada

    Kerry S. Courneya

  8. Department of Internal Medicine, NM Health Sciences Center, University of New Mexico, Albuquerque, NM, USA

    Linda S. Cook

  9. Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Holy Cross Centre, Room 514, Box ACB, 2210 2nd Street S.W., Calgary, AB, T2S 3C3, Canada

    Christine M. Friedenreich

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  1. Christine M. Friedenreich
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  2. Jeroen W. G. Derksen
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  7. Linda S. Cook
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Contributions

The study was designed and funding was obtained by CMF, KSC, and LSC. The data collection was overseen by CMF and LSC. The statistical analyses were done by TS and overseen by CMF, DRB, and JWGD. Manuscript preparation was done by JWGD, DRB, and CMF. Final manuscript review and approval was done by all authors.

Corresponding author

Correspondence to Christine M. Friedenreich.

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Friedenreich, C.M., Derksen, J.W.G., Speidel, T. et al. Case–control study of endogenous sex steroid hormones and risk of endometrial cancer. Cancer Causes Control 31, 161–171 (2020). https://doi.org/10.1007/s10552-019-01260-5

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