title: History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium.
abstract: OBJECTIVE
  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.
authors.affiliation: Deparment of Cancer Prevention and Control, Roswell Park Cancer Institute, A-352 Carlton House, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors.forename: Albina N
authors.initials: AN
authors.lastname: Minlikeeva
authors.affiliation: Deparment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
authors.affiliation: Deparment of Cancer Prevention and Control, Roswell Park Cancer Institute, A-352 Carlton House, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors.forename: Rikki A
authors.initials: RA
authors.lastname: Cannioto
authors.affiliation: Department of Surgery, Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: J Brian
authors.initials: JB
authors.lastname: Szender
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
authors.affiliation: Department of Epidemiology, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.|Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology and Reproductive Sciences and Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Francesmary
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authors.lastname: Modugno
authors.affiliation: The University of Texas, School of Public Health, Houston, TX, USA.
authors.forename: Roberta B
authors.initials: RB
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authors.affiliation: Deparment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: LaMonte
authors.affiliation: Deparment of Cancer Prevention and Control, Roswell Park Cancer Institute, A-352 Carlton House, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Friel
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.|Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Brahm H
authors.initials: BH
authors.lastname: Segal
authors.affiliation: Department of Surgery, Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.|Center of Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kunle
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authors.lastname: Odunsi
authors.affiliation: Department of Surgery, Division of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
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authors.affiliation: Center of Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA.
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authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Barbara
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authors.lastname: Schmalfeldt
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hanover, Lower Saxony, Germany.
authors.forename: Rüdiger
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authors.lastname: Klapdor
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hanover, Lower Saxony, Germany.
authors.forename: Thilo
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authors.lastname: Dӧrk
authors.affiliation: Department of Obstetrics and Gynecology, Hannover Medical School, Hanover, Lower Saxony, Germany.
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authors.lastname: Hillemanns
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Linda E
authors.initials: LE
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authors.affiliation: Department of Pathology and Laboratory Medicine, Foothills Medical Center, University of Calgary, Calgary, AB, Canada.
authors.forename: Martin
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authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Royal Alexandra Hospital, Edmonton, AB, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Steed
authors.affiliation: Department of Gynecological Oncology, Westmead Hospital and the Westmead Millenium Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: de Fazio
authors.affiliation: Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Jordan
authors.affiliation: Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.|School of Public Health, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Nagle
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
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authors.initials: HA
authors.lastname: Risch
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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authors.initials: MA
authors.lastname: Rossing
authors.affiliation: Department of Epidemiology, The Geisel School of Medicine at Dartmouth Medical, Hanover, NH, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doherty
authors.affiliation: Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.affiliation: Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology and Reproductive Sciences and Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robert
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authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
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authors.affiliation: Department of Gynecological Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
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authors.affiliation: Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Beth Y
authors.initials: BY
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authors.affiliation: Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.|Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjær
authors.affiliation: Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.|Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Høgdall
authors.affiliation: Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Allan
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authors.affiliation: Department of Public Health Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Joellen M
authors.initials: JM
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authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA.
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authors.initials: KL
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authors.affiliation: Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA.
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authors.initials: DW
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authors.affiliation: Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.affiliation: New Jersey Department of Health and Senior Services, Trenton, NJ, USA.|School of Public Health, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Paddock
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, and Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Lambertus A
authors.initials: LA
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authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, and Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Leon F
authors.initials: LF
authors.lastname: Massuger
authors.affiliation: Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kupryjanczyk
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.|University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Brenda
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authors.lastname: Diergaarde
authors.affiliation: Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.affiliation: 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.|Deparment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA. kirsten.moysich@roswellpark.org.|Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA. kirsten.moysich@roswellpark.org.
authors.forename: Kirsten B
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authors.lastname: Moysich
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000188:drug therapy; D018572:Disease-Free Survival; D005260:Female; D006331:Heart Diseases / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000150:complications / Q000401:mortality* / Q000473:pathology; D012306:Risk; D015996:Survival Rate
chemical_list: D000319:Adrenergic beta-Antagonists; D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Beta blockers; Diabetes; Hypertension; Medications; Mortality; Ovarian cancer prognosis