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

Albina N Minlikeeva¹, Jo L Freudenheim², Rikki A Cannioto¹, J Brian Szender³, Kevin H Eng⁴, Francesmary Modugno^{5

6

7}, Roberta B Ness⁸, Michael J LaMonte², Grace Friel¹, Brahm H Segal^{9

10}, Kunle Odunsi^{3

11}, Paul Mayor³, Emese Zsiros¹¹, Barbara Schmalfeldt¹², Rüdiger Klapdor¹³, Thilo Dӧrk¹³, Peter Hillemanns¹³, Linda E Kelemen¹⁴, Martin Kӧbel¹⁵, Helen Steed¹⁶, Anna de Fazio¹⁷; Australian Ovarian Cancer Study Group; Susan J Jordan¹⁸, Christina M Nagle^{18

19}, Harvey A Risch²⁰, Mary Anne Rossing²¹, Jennifer A Doherty²², Marc T Goodman²³, Robert Edwards^{6

7}, Keitaro Matsuo²⁴, Mika Mizuno²⁵, Beth Y Karlan²⁶, Susanne K Kjær^{27

28}, Estrid Høgdall^{27

29}, Allan Jensen²⁷, Joellen M Schildkraut³⁰, Kathryn L Terry³¹, Daniel W Cramer³¹, Elisa V Bandera³², Lisa E Paddock^{33

34}, Lambertus A Kiemeney³⁵, Leon F Massuger³⁵, Jolanta Kupryjanczyk³⁶, Andrew Berchuck³⁷, Jenny Chang-Claude^{38

39}, Brenda Diergaarde⁴⁰, Penelope M Webb¹⁸, Kirsten B Moysich^{41

42

43}; Ovarian Cancer Association Consortium

Affiliations

¹ Deparment of Cancer Prevention and Control, Roswell Park Cancer Institute, A-352 Carlton House, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
² Deparment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
³ Department of Surgery, Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁴ Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁵ Department of Epidemiology, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
⁶ Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
⁷ Department of Obstetrics, Gynecology and Reproductive Sciences and Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ The University of Texas, School of Public Health, Houston, TX, USA.
⁹ Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹⁰ Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹¹ Center of Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹² Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹³ Department of Obstetrics and Gynecology, Hannover Medical School, Hanover, Lower Saxony, Germany.
¹⁴ Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada.
¹⁶ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Royal Alexandra Hospital, Edmonton, AB, Canada.
¹⁷ Department of Gynecological Oncology, Westmead Hospital and the Westmead Millenium Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
¹⁸ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
¹⁹ School of Public Health, The University of Queensland, Brisbane, QLD, Australia.
²⁰ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
²¹ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
²² Department of Epidemiology, The Geisel School of Medicine at Dartmouth Medical, Hanover, NH, USA.
²³ Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
²⁴ Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
²⁵ Department of Gynecological Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
²⁶ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
²⁷ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
²⁸ Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
²⁹ Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
³⁰ Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
³¹ Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA.
³² Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
³³ New Jersey Department of Health and Senior Services, Trenton, NJ, USA.
³⁴ School of Public Health, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA.
³⁵ Radboud University Medical Center, Radboud Institute for Health Sciences, and Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
³⁶ Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
³⁷ Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
³⁸ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
³⁹ University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴⁰ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
⁴¹ Deparment of Cancer Prevention and Control, Roswell Park Cancer Institute, A-352 Carlton House, Elm and Carlton Streets, Buffalo, NY, 14263, USA. kirsten.moysich@roswellpark.org.
⁴² Deparment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA. kirsten.moysich@roswellpark.org.
⁴³ Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA. kirsten.moysich@roswellpark.org.

PMID: 28293802
PMCID: PMC5500209
DOI: 10.1007/s10552-017-0867-1

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

Albina N Minlikeeva et al. Cancer Causes Control. 2017 May.

. 2017 May;28(5):469-486.

doi: 10.1007/s10552-017-0867-1. Epub 2017 Mar 14.

Authors

Affiliations

¹ Deparment of Cancer Prevention and Control, Roswell Park Cancer Institute, A-352 Carlton House, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
² Deparment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
³ Department of Surgery, Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁴ Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁵ Department of Epidemiology, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
⁶ Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
⁷ Department of Obstetrics, Gynecology and Reproductive Sciences and Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ The University of Texas, School of Public Health, Houston, TX, USA.
⁹ Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹⁰ Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹¹ Center of Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹² Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹³ Department of Obstetrics and Gynecology, Hannover Medical School, Hanover, Lower Saxony, Germany.
¹⁴ Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
¹⁵ Department of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada.
¹⁶ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Royal Alexandra Hospital, Edmonton, AB, Canada.
¹⁷ Department of Gynecological Oncology, Westmead Hospital and the Westmead Millenium Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
¹⁸ Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
¹⁹ School of Public Health, The University of Queensland, Brisbane, QLD, Australia.
²⁰ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
²¹ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
²² Department of Epidemiology, The Geisel School of Medicine at Dartmouth Medical, Hanover, NH, USA.
²³ Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
²⁴ Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
²⁵ Department of Gynecological Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
²⁶ Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
²⁷ Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
²⁸ Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
²⁹ Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
³⁰ Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
³¹ Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA.
³² Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
³³ New Jersey Department of Health and Senior Services, Trenton, NJ, USA.
³⁴ School of Public Health, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA.
³⁵ Radboud University Medical Center, Radboud Institute for Health Sciences, and Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
³⁶ Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
³⁷ Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
³⁸ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
³⁹ University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴⁰ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
⁴¹ Deparment of Cancer Prevention and Control, Roswell Park Cancer Institute, A-352 Carlton House, Elm and Carlton Streets, Buffalo, NY, 14263, USA. kirsten.moysich@roswellpark.org.
⁴² Deparment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA. kirsten.moysich@roswellpark.org.
⁴³ Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA. kirsten.moysich@roswellpark.org.

PMID: 28293802
PMCID: PMC5500209
DOI: 10.1007/s10552-017-0867-1

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.

Keywords: Beta blockers; Diabetes; Hypertension; Medications; Mortality; Ovarian cancer prognosis.

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Conflict of interest statement

Compliance with Ethical Standards

Conflict of interest All the authors declare no conflict of interest.

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

Affiliations

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

Authors

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Abstract

Conflict of interest statement

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