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History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium

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Abstract

Purpose

Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype.

Methods

Using pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes.

Results

History of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01–1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88–1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87–1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35–0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03–1.40, HR = 1.28; 95% CI = 1.05–1.55, and HR = 1.63; 95% CI = 1.20–2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53–0.94.

Conclusions

Histories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients. Understanding mechanisms for these observations could provide insight regarding treatment.

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Acknowledgments

AOV study center thanks Jennifer Koziak, Mie Konno, Michelle Darago, Faye Chambers, and the Tom Baker Cancer Centre Translational Laboratories. The Australian Ovarian Cancer Study Management Group (D. Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green, P. Webb) and ACS Investigators (A. Green, P. Parsons, N. Hayward, P. Webb, D. Whiteman) thank all the clinical and scientific collaborators (see http://www.aocstudy.org/) and the women for their contribution. The German Ovarian Cancer Study (GER) center thanks Ursula Eilber for competent technical assistance.

Funding

A.N. Minlikeeva was supported by National Cancer Institute (NCI) Interdisciplinary Training Grant in Cancer Epidemiology R25CA113951; J. L. Freudenheim was supported by National Institute of Health (NIH)/NCI (2R25CA113951); G. Friel was supported by NIH/NCI (R01CA095023 and R01CA126841); K.H.Eng was supported by NIH/NLM (K01LM012100) and the Roswell Park Alliance Foundation; J.B. Szender was supported by 5T32CA108456; B.H. Segal was supported by NIH (R01CA188900); K.B. Moysich was supported by NIH/NCI (2R25CA113951, R01CA095023, R01CA126841, P50CA159981) and the Roswell Park Alliance Foundation; AOV was supported by the Canadian Institutes for Health Research (MOP-86727); AUS was supported by U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania, and Cancer Foundation of Western Australia; CON was supported by NIH (R01-CA074850 and R01-CA080742); DOV was supported by NIH (R01-CA112523 and R01-CA87538); GER was supported by German Federal Ministry of Education and Research, Program of Clinical Biomedical Research (01GB9401), and German Cancer Research Center; HAW was supported by NIH (R01-CA58598, N01-CN-55424, and N01-PC-67001); HOP was supported by the Department of Defense (DOD): DAMD17-02-1-0669 and NIH/NCI (K07-CA080668, R01-CA95023, P50-CA159981, and R01-CA126841); JPN was supported by Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare; LAX was supported by American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; MAL was supported by NIH/NCI (R01-CA61107), Danish Cancer Society (research grant 94 222 52), and the Mermaid I project; NCO was supported by NIH (R01-CA76016) and the DOD (DAMD17-02-1-0666); NEC was supported by NIH (R01-CA54419 and P50-CA105009) and DOD (W81XWH-10-1-02802); NJO was supported by NIH/NCI (K07 CA095666, K22-CA138563, and P30-CA072720) and the Cancer Institute of New Jersey; NTH was supported by Radboud University Medical Centre; WOC was supported by Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27), The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

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Authors and Affiliations

  1. Deparment of Cancer Prevention and Control, Roswell Park Cancer Institute, A-352 Carlton House, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Albina N. Minlikeeva, Rikki A. Cannioto, Grace Friel & Kirsten B. Moysich

  2. Deparment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA

    Jo L. Freudenheim, Michael J. LaMonte & Kirsten B. Moysich

  3. Department of Surgery, Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA

    J. Brian Szender, Kunle Odunsi & Paul Mayor

  4. Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA

    Kevin H. Eng

  5. Department of Epidemiology, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Francesmary Modugno

  6. Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Francesmary Modugno & Robert Edwards

  7. Department of Obstetrics, Gynecology and Reproductive Sciences and Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA

    Francesmary Modugno & Robert Edwards

  8. The University of Texas, School of Public Health, Houston, TX, USA

    Roberta B. Ness

  9. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    Brahm H. Segal

  10. Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA

    Brahm H. Segal & Kirsten B. Moysich

  11. Center of Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA

    Kunle Odunsi & Emese Zsiros

  12. Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Barbara Schmalfeldt

  13. Department of Obstetrics and Gynecology, Hannover Medical School, Hanover, Lower Saxony, Germany

    Rüdiger Klapdor, Thilo Dӧrk & Peter Hillemanns

  14. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA

    Linda E. Kelemen

  15. Department of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada

    Martin Kӧbel

  16. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Royal Alexandra Hospital, Edmonton, AB, Canada

    Helen Steed

  17. Department of Gynecological Oncology, Westmead Hospital and the Westmead Millenium Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia

    Anna de Fazio

  18. Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

    Susan J. Jordan, Christina M. Nagle & Penelope M. Webb

  19. School of Public Health, The University of Queensland, Brisbane, QLD, Australia

    Christina M. Nagle

  20. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA

    Harvey A. Risch

  21. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Mary Anne Rossing

  22. Department of Epidemiology, The Geisel School of Medicine at Dartmouth Medical, Hanover, NH, USA

    Jennifer A. Doherty

  23. Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Marc T. Goodman

  24. Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan

    Keitaro Matsuo

  25. Department of Gynecological Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan

    Mika Mizuno

  26. Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Beth Y. Karlan

  27. Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark

    Susanne K. Kjær, Estrid Høgdall & Allan Jensen

  28. Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Susanne K. Kjær

  29. Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark

    Estrid Høgdall

  30. Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA

    Joellen M. Schildkraut

  31. Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital, Boston, MA, USA

    Kathryn L. Terry & Daniel W. Cramer

  32. Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Elisa V. Bandera

  33. New Jersey Department of Health and Senior Services, Trenton, NJ, USA

    Lisa E. Paddock

  34. School of Public Health, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA

    Lisa E. Paddock

  35. Radboud University Medical Center, Radboud Institute for Health Sciences, and Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands

    Lambertus A. Kiemeney & Leon F. Massuger

  36. Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

    Jolanta Kupryjanczyk

  37. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA

    Andrew Berchuck

  38. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany

    Jenny Chang-Claude

  39. University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Jenny Chang-Claude

  40. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Brenda Diergaarde

Authors
  1. Albina N. Minlikeeva
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  2. Jo L. Freudenheim
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  3. Rikki A. Cannioto
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  40. Lambertus A. Kiemeney
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  47. Kirsten B. Moysich
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Consortia

on behalf of the Australian Ovarian Cancer Study Group

on behalf of the Ovarian Cancer Association Consortium

Corresponding author

Correspondence to Kirsten B. Moysich.

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All the authors declare no conflict of interest.

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Minlikeeva, A.N., Freudenheim, J.L., Cannioto, R.A. et al. History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium. Cancer Causes Control 28, 469–486 (2017). https://doi.org/10.1007/s10552-017-0867-1

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  • DOI: https://doi.org/10.1007/s10552-017-0867-1

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