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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Most cited references 41

Record: found
Abstract: found
Article: not found

Stress hormone-mediated invasion of ovarian cancer cells.

Premal H. Thaker, Charles N. Landen, Yang Li … (2006)

There is growing evidence that stress and other behavioral factors may affect cancer progression and patient survival. The underlying mechanisms for this association are poorly understood. The purpose of this study is to determine the effects of stress-associated hormones norepinephrine, epinephrine, and cortisol on the invasive potential of ovarian cancer cells. The ovarian cancer cells EG, SKOV3, and 222 were exposed to increasing levels of either norepinephrine, epinephrine, or cortisol, and the in vitro invasive potential was determined using the membrane invasion culture system. Additionally, the effects of these stress hormones on matrix metalloproteinase-2 (MMP-2) and MMP-9 were determined by ELISA. The effects of the beta-adrenergic agonist isoproterenol on in vivo tumor growth were determined using nude mice. Stress levels of norepinephrine increased the in vitro invasiveness of ovarian cancer cells by 89% to 198%. Epinephrine also induced significant increases in invasion in all three cell lines ranging from 64% to 76%. Cortisol did not significantly affect invasiveness of the EG and 222 cell lines but increased invasion in the SKOV3 cell line (P = 0.01). We have previously shown that ovarian cancer cells express beta-adrenergic receptors. The beta-adrenergic antagonist propanolol (1 mumol/L) completely blocked the norepinephrine-induced increase in invasiveness. Norepinephrine also increased tumor cell expression of MMP-2 (P = 0.02 for both SKOV3 and EG cells) and MMP-9 (P = 0.01 and 0.04, respectively), and pharmacologic blockade of MMPs abrogated the effects of norepinephrine on tumor cell invasive potential. Isoproterenol treatment resulted in a significant increase in tumor volume and infiltration in the SKOV3ip1 in vivo model, which was blocked by propranolol. These findings provide direct experimental evidence that stress hormones can enhance the invasive potential of ovarian cancer cells. These effects are most likely mediated by stimulation of MMPs.

0 comments Cited 141 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis.

H R Haak, M W Dercksen, Chantal Heijnen … (2007)

The purpose of this study was to document the prevalence of diabetes among newly diagnosed cancer patients and to evaluate the influence of diabetes on stage at diagnosis, treatment and overall survival. We performed a population-based analyses of all 58,498 cancer patients newly diagnosed between 1995 and 2002 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by hospital medical records review. Follow-up of all patients was completed until January 1, 2005. Nine percent of all cancer patients had diabetes at the time of cancer diagnosis. The prevalence of diabetes was highest among patients with cancer of the pancreas (19%), uterus (14%) and among young men with kidney cancer (8%). Colon, breast and ovarian cancer patients with diabetes were more often diagnosed with a higher tumour stage (p < 0.05). Patients with diabetes and cancer of the oesophagus, colon, breast and ovary were treated less aggressively compared to those without diabetes (p < 0.05). During the follow-up period 3,902 of 5,555 cancer patients with diabetes died and 29,909 of 52,943 cancer patients without diabetes died. For all cancers combined, in a multivariate cox-regression model, adjusting for age, gender, stage, treatment and cardiovascular disease, patients with diabetes experienced a significant increase in overall mortality (HR = 1.44, 95% CI 1.40-1.49), ranging however from 0 to 40% for different types of cancer, compared to those without diabetes. In conclusion, diabetic cancer patients frequently were treated less aggressively and had a worse prognosis compared to those without diabetes. (c) 2007 Wiley-Liss, Inc.

0 comments Cited 109 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project.

Björn Lindkvist, Tanja Stocks, Jonas Manjer … (2012)

Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment: 1.07 [95% CI: 1.04-1.09]) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI: 1.08-1.15) for men and 1.06 (95% CI: 1.02-1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women.

0 comments Cited 101 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-journal-id): 9100846

Journal ID (pubmed-jr-id): 1173

Journal ID (nlm-ta): Cancer Causes Control

Journal ID (iso-abbrev): Cancer Causes Control

Title: Cancer causes & control : CCC

ISSN (Print): 0957-5243

ISSN (Electronic): 1573-7225

Publication date Nihms-submitted: 19 April 2017

Publication date (Electronic): 14 March 2017

Publication date (Print): May 2017

Publication date PMC-release: 01 May 2018

Volume: 28

Issue: 5

Pages: 469-486

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

Article

Accession ID: PMC5500209 Pmcid ID: PMC5500209 Pmc-uid ID: 5500209 Manuscript ID: nihpa868294

DOI: 10.1007/s10552-017-0867-1

PMC ID: 5500209

PubMed ID: 28293802

SO-VID: c32fb953-33df-4a78-9f17-7b430e618da1

History

Comments

Comment on this article

scite_

Cited by 16

See all cited by

Most referenced authors 1,617

See all reference authors

- Version 1
- Version 1

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

Read this article at

Abstract

Purpose

Methods

Results

Conclusions

Related collections

Bioscientifica Open Endocrinology

Most cited references 41

Stress hormone-mediated invasion of ovarian cancer cells.

Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis.

Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project.

Author and article information

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 367

Cited by 16

Most referenced authors 1,617