Cancer Causes & Control

, Volume 28, Issue 5, pp 469–486

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

  • Albina N. Minlikeeva
  • Jo L. Freudenheim
  • Rikki A. Cannioto
  • J. Brian Szender
  • Kevin H. Eng
  • Francesmary Modugno
  • Roberta B. Ness
  • Michael J. LaMonte
  • Grace Friel
  • Brahm H. Segal
  • Kunle Odunsi
  • Paul Mayor
  • Emese Zsiros
  • Barbara Schmalfeldt
  • Rüdiger Klapdor
  • Thilo Dӧrk
  • Peter Hillemanns
  • Linda E. Kelemen
  • Martin Kӧbel
  • Helen Steed
  • Anna de Fazio
  • on behalf of the Australian Ovarian Cancer Study Group
  • Susan J. Jordan
  • Christina M. Nagle
  • Harvey A. Risch
  • Mary Anne Rossing
  • Jennifer A. Doherty
  • Marc T. Goodman
  • Robert Edwards
  • Keitaro Matsuo
  • Mika Mizuno
  • Beth Y. Karlan
  • Susanne K. Kjær
  • Estrid Høgdall
  • Allan Jensen
  • Joellen M. Schildkraut
  • Kathryn L. Terry
  • Daniel W. Cramer
  • Elisa V. Bandera
  • Lisa E. Paddock
  • Lambertus A. Kiemeney
  • Leon F. Massuger
  • Jolanta Kupryjanczyk
  • Andrew Berchuck
  • Jenny Chang-Claude
  • Brenda Diergaarde
  • Penelope M. Webb
  • Kirsten B. Moysich
  • on behalf of the Ovarian Cancer Association Consortium
Original paper

DOI: 10.1007/s10552-017-0867-1

Cite this article as:
Minlikeeva, A.N., Freudenheim, J.L., Cannioto, R.A. et al. Cancer Causes Control (2017) 28: 469. 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

Ovarian cancer prognosis Hypertension Diabetes Medications Mortality Beta blockers 

Funding information

Funder NameGrant NumberFunding Note
German Cancer Research Center
    Cancer Foundation of Western Australia
      The Maria Sklodowska-Curie Memorial Center and Institute of Oncology
        Polish Ministry of Science and Higher Education
        • 2PO5A06827
        • 4PO5C02814
        Radboud University Medical Center
          Cancer Institute of New Jersey
            National Cancer Institute
            • P30CA072720
            • K22CA138563
            • K07 CA095666
            • P50CA105009
            • R01CA54419
            • R01CA76016
            • R01CA61107
            • R01CA126841
            • P50CA159981
            • R0195023
            • K07CA080668
            • R25CA113951
            U.S. Department of Defense
            • W81XWH10102802
            • DAMD170210666
            • DAMD170210669
            Mermaid I project
              Danish Cancer Society
              • 9422252
              National Center for Advancing Translational Sciences
              • UL1TR000124
              American Cancer Society
              • SIOP0625801 COUN
              Ministry of Health Labour and Welfare
                National Institutes of Health
                • N01PC67001
                • N01CN55424
                • R01CA58598
                • R01CA87538
                • R01CA112523
                • R01CA080742
                • R01CA074850
                • P50CA159981
                • R01CA188900
                • 5T32CA108456
                • K01LM012100
                • R01CA126841
                • R01CA095023
                • 2R25CA113951
                German Federal Ministry of Education and Research
                • 01GB9401
                Cancer Councils of New South Wales
                  National Health and Medical Research Council
                  • 199600 and 400281
                  US Army Medical Research and Materiel Command
                  • DAMD170110729
                  Canadian Institutes of Health Research
                  • MOP-86727
                  Roswell Park Alliance Foundation, Roswell Park Cancer Institute

                    Copyright information

                    © Springer International Publishing Switzerland 2017

                    Authors and Affiliations

                    • Albina N. Minlikeeva
                      • 1
                    • Jo L. Freudenheim
                      • 2
                    • Rikki A. Cannioto
                      • 1
                    • J. Brian Szender
                      • 3
                    • Kevin H. Eng
                      • 4
                    • Francesmary Modugno
                      • 5
                      • 6
                      • 7
                    • Roberta B. Ness
                      • 8
                    • Michael J. LaMonte
                      • 2
                    • Grace Friel
                      • 1
                    • Brahm H. Segal
                      • 9
                      • 10
                    • Kunle Odunsi
                      • 3
                      • 11
                    • Paul Mayor
                      • 3
                    • Emese Zsiros
                      • 11
                    • Barbara Schmalfeldt
                      • 12
                    • Rüdiger Klapdor
                      • 13
                    • Thilo Dӧrk
                      • 13
                    • Peter Hillemanns
                      • 13
                    • Linda E. Kelemen
                      • 14
                    • Martin Kӧbel
                      • 15
                    • Helen Steed
                      • 16
                    • Anna de Fazio
                      • 17
                    • on behalf of the Australian Ovarian Cancer Study Group
                    • Susan J. Jordan
                      • 18
                    • Christina M. Nagle
                      • 18
                      • 19
                    • Harvey A. Risch
                      • 20
                    • Mary Anne Rossing
                      • 21
                    • Jennifer A. Doherty
                      • 22
                    • Marc T. Goodman
                      • 23
                    • Robert Edwards
                      • 6
                      • 7
                    • Keitaro Matsuo
                      • 24
                    • Mika Mizuno
                      • 25
                    • Beth Y. Karlan
                      • 26
                    • Susanne K. Kjær
                      • 27
                      • 28
                    • Estrid Høgdall
                      • 27
                      • 29
                    • Allan Jensen
                      • 27
                    • Joellen M. Schildkraut
                      • 30
                    • Kathryn L. Terry
                      • 31
                    • Daniel W. Cramer
                      • 31
                    • Elisa V. Bandera
                      • 32
                    • Lisa E. Paddock
                      • 33
                      • 34
                    • Lambertus A. Kiemeney
                      • 35
                    • Leon F. Massuger
                      • 35
                    • Jolanta Kupryjanczyk
                      • 36
                    • Andrew Berchuck
                      • 37
                    • Jenny Chang-Claude
                      • 38
                      • 39
                    • Brenda Diergaarde
                      • 40
                    • Penelope M. Webb
                      • 18
                    • Kirsten B. Moysich
                      • 1
                      • 2
                      • 10
                    • on behalf of the Ovarian Cancer Association Consortium
                    1. 1.Deparment of Cancer Prevention and ControlRoswell Park Cancer InstituteBuffaloUSA
                    2. 2.Deparment of Epidemiology and Environmental HealthUniversity at BuffaloBuffaloUSA
                    3. 3.Department of Surgery, Division of Gynecologic OncologyRoswell Park Cancer InstituteBuffaloUSA
                    4. 4.Department of Biostatistics and BioinformaticsRoswell Park Cancer InstituteBuffaloUSA
                    5. 5.Department of EpidemiologyUniversity of Pittsburgh, and University of Pittsburgh Cancer InstitutePittsburghUSA
                    6. 6.Ovarian Cancer Center of Excellence, Womens Cancer Research ProgramMagee-Womens Research Institute and University of Pittsburgh Cancer InstitutePittsburghUSA
                    7. 7.Department of Obstetrics, Gynecology and Reproductive Sciences and Department of EpidemiologyUniversity of PittsburghPittsburghUSA
                    8. 8.The University of Texas, School of Public HealthHoustonUSA
                    9. 9.Department of MedicineRoswell Park Cancer InstituteBuffaloUSA
                    10. 10.Department of ImmunologyRoswell Park Cancer InstituteBuffaloUSA
                    11. 11.Center of ImmunotherapyRoswell Park Cancer InstituteBuffaloUSA
                    12. 12.Department of GynecologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
                    13. 13.Department of Obstetrics and GynecologyHannover Medical SchoolHanoverGermany
                    14. 14.Department of Public Health SciencesMedical University of South CarolinaCharlestonUSA
                    15. 15.Department of Pathology and Laboratory MedicineFoothills Medical Center, University of CalgaryCalgaryCanada
                    16. 16.Division of Gynecologic Oncology, Department of Obstetrics and GynecologyRoyal Alexandra HospitalEdmontonCanada
                    17. 17.Department of Gynecological Oncology, Westmead Hospital and the Westmead Millenium Institute for Medical ResearchThe University of SydneySydneyAustralia
                    18. 18.Population Health DepartmentQIMR Berghofer Medical Research InstituteBrisbaneAustralia
                    19. 19.School of Public Health, The University of QueenslandBrisbaneAustralia
                    20. 20.Department of Chronic Disease EpidemiologyYale School of Public HealthNew HavenUSA
                    21. 21.Program in Epidemiology, Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
                    22. 22.Department of EpidemiologyThe Geisel School of Medicine at Dartmouth MedicalHanoverUSA
                    23. 23.Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesUSA
                    24. 24.Division of Molecular MedicineAichi Cancer Center Research InstituteNagoyaJapan
                    25. 25.Department of Gynecological OncologyAichi Cancer Center HospitalNagoyaJapan
                    26. 26.Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesUSA
                    27. 27.Department of Virus, Lifestyle and GenesDanish Cancer Society Research CenterCopenhagenDenmark
                    28. 28.Department of Gynaecology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
                    29. 29.Department of Pathology, Herlev HospitalUniversity of CopenhagenCopenhagenDenmark
                    30. 30.Department of Public Health Sciences, School of MedicineUniversity of VirginiaCharlottesvilleUSA
                    31. 31.Obstetrics and Gynecology Epidemiology CenterBrigham and Women’s HospitalBostonUSA
                    32. 32.Cancer Prevention and Control ProgramRutgers Cancer Institute of New JerseyNew BrunswickUSA
                    33. 33.New Jersey Department of Health and Senior ServicesTrentonUSA
                    34. 34.School of Public HealthUniversity of Medicine and Dentistry of New JerseyPiscatawayUSA
                    35. 35.Radboud University Medical Center, Radboud Institute for Health Sciences, and Radboud Institute for Molecular Life SciencesNijmegenThe Netherlands
                    36. 36.Department of Pathology and Laboratory DiagnosticsThe Maria Sklodowska-Curie Memorial Cancer Center and Institute of OncologyWarsawPoland
                    37. 37.Department of Obstetrics and GynecologyDuke University Medical CenterDurhamUSA
                    38. 38.Division of Cancer EpidemiologyGerman Cancer Research CenterHeidelbergGermany
                    39. 39.University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-EppendorfHamburgGermany
                    40. 40.Department of Epidemiology, Graduate School of Public HealthUniversity of Pittsburgh, and University of Pittsburgh Cancer InstitutePittsburghUSA

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