Statin use is associated with improved surviva lin ovarian cancer: A retrospective population based study

Alexandra Couttenier; Olivia Lacroix; Evelien Vaes; Chris R. Cardwell; Harlinde De Schutter; Annie Robert

doi:10.1371/journal.pone.0189233

Statin use is associated with improved surviva lin ovarian cancer: A retrospective population based study

Alexandra Couttenier^*, Olivia Lacroix, Evelien Vaes, Chris R. Cardwell, Harlinde De Schutter, Annie Robert

^*Corresponding author for this work

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Abstract

Background: Preclinical in vitro and in vivo studies suggest that statins could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether statin use is associated with improved survival in ovarian cancer patients at the Belgian population-level. Methods: All patients with invasive epithelial ovarian cancer diagnosed between 2004 and 2012 were identified from the Belgian Cancer Registry. Vital statuses were obtained from the Crossroads Bank for Social Security and ovarian cancer-specific deaths were identified from death certificates provided by regional administrations. Information on cancer treatments and statin use were retrieved from health insurance databases. Statin use was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HR) and 95% confidence intervals (95%CI) for the association between postdiagnostic exposure to statins and overall- or ovarian cancer-specific mortality within three years after diagnosis. Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments. Results: A total of 5,416 patients with epithelial ovarian cancer met the inclusion criteria. Of these 1,255 (23%) had at least one statin prescription within three years after diagnosis. Postdiag-nostic use of statins was associated with a reduced risk of overall mortality (adjusted HR = 0.81, 95%CI:0.72–0.90, p<0.001). In analyses by statin type, this association was only significant for simvastatin (adjusted HR = 0.86, 95%CI:0.74–0.99, p = 0.05) or rosuvastatin (adjusted HR = 0.71, 95%CI:0.55–0.92, p = 0.01). In subgroup analyses by statin prediagnostic use, the protective association for postdiagnostic statin use was only observed in patients who were also using statins before diagnosis (adjusted HR = 0.73, 95%CI:0.64–0.83, p<0.001). Similar results were observed for ovarian cancer-specific mortality. Conclusion: In this large nation-wide cohort of ovarian cancer patients postdiagnostic use of statins was associated with improved survival.

Original language	English
Article number	e0189233
Number of pages	14
Journal	PLoS ONE
Volume	12
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0189233
Publication status	Published - 19 Dec 2017

Bibliographical note

Funding Information:
Alexandra Couttenier and Olivia Lacroix are fully funded by grants of Université catholique de Louvain - Institut de Recherche Expérimentale et Clinique - Pôle d’Epidémiologie et Biostatistique, via grant numbers UCL-2015-EPID-2022 and UCL-2015-EPID-2019, respectively. We confirm that we did not receive any additional funding for this study. We thank all the staff of the Belgian Cancer registry and all physicians, pathologists and data managers involved in Cancer Registration in Belgium for their dedicated data collection. We also acknowledge the Intermutualistic Agency (IMA) for providing health insurance data; the Crossroads Bank for Social Security (BCBSS) for providing vital statuses; the Belgian regional authorities for providing causes of death. We also sincerely thank Anne Kongs, MD (Agentschap Zorg and Gezondheid, Brussels, Begium) and Una Mc Menamin, PhD (Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland) for editorial assistance.

Publisher Copyright:
© 2017 Couttenier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
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10.1371/journal.pone.0189233Licence: CC BY

Statin use is associated with improved survival in ovarian cancer: A retrospective population-based study
Copyright 2017 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 3.9 MBLicence: CC BY

Cite this

@article{c9deb133b418480ab6db7a8f3d422780,

title = "Statin use is associated with improved surviva lin ovarian cancer: A retrospective population based study",

abstract = "Background: Preclinical in vitro and in vivo studies suggest that statins could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether statin use is associated with improved survival in ovarian cancer patients at the Belgian population-level. Methods: All patients with invasive epithelial ovarian cancer diagnosed between 2004 and 2012 were identified from the Belgian Cancer Registry. Vital statuses were obtained from the Crossroads Bank for Social Security and ovarian cancer-specific deaths were identified from death certificates provided by regional administrations. Information on cancer treatments and statin use were retrieved from health insurance databases. Statin use was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HR) and 95% confidence intervals (95%CI) for the association between postdiagnostic exposure to statins and overall- or ovarian cancer-specific mortality within three years after diagnosis. Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments. Results: A total of 5,416 patients with epithelial ovarian cancer met the inclusion criteria. Of these 1,255 (23%) had at least one statin prescription within three years after diagnosis. Postdiag-nostic use of statins was associated with a reduced risk of overall mortality (adjusted HR = 0.81, 95%CI:0.72–0.90, p<0.001). In analyses by statin type, this association was only significant for simvastatin (adjusted HR = 0.86, 95%CI:0.74–0.99, p = 0.05) or rosuvastatin (adjusted HR = 0.71, 95%CI:0.55–0.92, p = 0.01). In subgroup analyses by statin prediagnostic use, the protective association for postdiagnostic statin use was only observed in patients who were also using statins before diagnosis (adjusted HR = 0.73, 95%CI:0.64–0.83, p<0.001). Similar results were observed for ovarian cancer-specific mortality. Conclusion: In this large nation-wide cohort of ovarian cancer patients postdiagnostic use of statins was associated with improved survival.",

author = "Alexandra Couttenier and Olivia Lacroix and Evelien Vaes and Cardwell, {Chris R.} and {De Schutter}, Harlinde and Annie Robert",

note = "Funding Information: Alexandra Couttenier and Olivia Lacroix are fully funded by grants of Universit{\'e} catholique de Louvain - Institut de Recherche Exp{\'e}rimentale et Clinique - P{\^o}le d{\textquoteright}Epid{\'e}miologie et Biostatistique, via grant numbers UCL-2015-EPID-2022 and UCL-2015-EPID-2019, respectively. We confirm that we did not receive any additional funding for this study. We thank all the staff of the Belgian Cancer registry and all physicians, pathologists and data managers involved in Cancer Registration in Belgium for their dedicated data collection. We also acknowledge the Intermutualistic Agency (IMA) for providing health insurance data; the Crossroads Bank for Social Security (BCBSS) for providing vital statuses; the Belgian regional authorities for providing causes of death. We also sincerely thank Anne Kongs, MD (Agentschap Zorg and Gezondheid, Brussels, Begium) and Una Mc Menamin, PhD (Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen{\textquoteright}s University Belfast, Belfast, Northern Ireland) for editorial assistance. Publisher Copyright: {\textcopyright} 2017 Couttenier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "2017",

month = dec,

day = "19",

doi = "10.1371/journal.pone.0189233",

language = "English",

volume = "12",

journal = "PLoS One",

issn = "1932-6203",

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TY - JOUR

T1 - Statin use is associated with improved surviva lin ovarian cancer: A retrospective population based study

AU - Couttenier, Alexandra

AU - Lacroix, Olivia

AU - Vaes, Evelien

AU - Cardwell, Chris R.

AU - De Schutter, Harlinde

AU - Robert, Annie

N1 - Funding Information: Alexandra Couttenier and Olivia Lacroix are fully funded by grants of Université catholique de Louvain - Institut de Recherche Expérimentale et Clinique - Pôle d’Epidémiologie et Biostatistique, via grant numbers UCL-2015-EPID-2022 and UCL-2015-EPID-2019, respectively. We confirm that we did not receive any additional funding for this study. We thank all the staff of the Belgian Cancer registry and all physicians, pathologists and data managers involved in Cancer Registration in Belgium for their dedicated data collection. We also acknowledge the Intermutualistic Agency (IMA) for providing health insurance data; the Crossroads Bank for Social Security (BCBSS) for providing vital statuses; the Belgian regional authorities for providing causes of death. We also sincerely thank Anne Kongs, MD (Agentschap Zorg and Gezondheid, Brussels, Begium) and Una Mc Menamin, PhD (Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland) for editorial assistance. Publisher Copyright: © 2017 Couttenier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2017/12/19

Y1 - 2017/12/19

N2 - Background: Preclinical in vitro and in vivo studies suggest that statins could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether statin use is associated with improved survival in ovarian cancer patients at the Belgian population-level. Methods: All patients with invasive epithelial ovarian cancer diagnosed between 2004 and 2012 were identified from the Belgian Cancer Registry. Vital statuses were obtained from the Crossroads Bank for Social Security and ovarian cancer-specific deaths were identified from death certificates provided by regional administrations. Information on cancer treatments and statin use were retrieved from health insurance databases. Statin use was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HR) and 95% confidence intervals (95%CI) for the association between postdiagnostic exposure to statins and overall- or ovarian cancer-specific mortality within three years after diagnosis. Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments. Results: A total of 5,416 patients with epithelial ovarian cancer met the inclusion criteria. Of these 1,255 (23%) had at least one statin prescription within three years after diagnosis. Postdiag-nostic use of statins was associated with a reduced risk of overall mortality (adjusted HR = 0.81, 95%CI:0.72–0.90, p<0.001). In analyses by statin type, this association was only significant for simvastatin (adjusted HR = 0.86, 95%CI:0.74–0.99, p = 0.05) or rosuvastatin (adjusted HR = 0.71, 95%CI:0.55–0.92, p = 0.01). In subgroup analyses by statin prediagnostic use, the protective association for postdiagnostic statin use was only observed in patients who were also using statins before diagnosis (adjusted HR = 0.73, 95%CI:0.64–0.83, p<0.001). Similar results were observed for ovarian cancer-specific mortality. Conclusion: In this large nation-wide cohort of ovarian cancer patients postdiagnostic use of statins was associated with improved survival.

AB - Background: Preclinical in vitro and in vivo studies suggest that statins could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether statin use is associated with improved survival in ovarian cancer patients at the Belgian population-level. Methods: All patients with invasive epithelial ovarian cancer diagnosed between 2004 and 2012 were identified from the Belgian Cancer Registry. Vital statuses were obtained from the Crossroads Bank for Social Security and ovarian cancer-specific deaths were identified from death certificates provided by regional administrations. Information on cancer treatments and statin use were retrieved from health insurance databases. Statin use was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HR) and 95% confidence intervals (95%CI) for the association between postdiagnostic exposure to statins and overall- or ovarian cancer-specific mortality within three years after diagnosis. Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments. Results: A total of 5,416 patients with epithelial ovarian cancer met the inclusion criteria. Of these 1,255 (23%) had at least one statin prescription within three years after diagnosis. Postdiag-nostic use of statins was associated with a reduced risk of overall mortality (adjusted HR = 0.81, 95%CI:0.72–0.90, p<0.001). In analyses by statin type, this association was only significant for simvastatin (adjusted HR = 0.86, 95%CI:0.74–0.99, p = 0.05) or rosuvastatin (adjusted HR = 0.71, 95%CI:0.55–0.92, p = 0.01). In subgroup analyses by statin prediagnostic use, the protective association for postdiagnostic statin use was only observed in patients who were also using statins before diagnosis (adjusted HR = 0.73, 95%CI:0.64–0.83, p<0.001). Similar results were observed for ovarian cancer-specific mortality. Conclusion: In this large nation-wide cohort of ovarian cancer patients postdiagnostic use of statins was associated with improved survival.

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DO - 10.1371/journal.pone.0189233

M3 - Article

C2 - 29261726

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JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e0189233

ER -

Statin use is associated with improved surviva lin ovarian cancer: A retrospective population based study

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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