Prognosis of ovarian cancer in women with type 2 diabetes using metformin and other forms of antidiabetic medication or statins: a retrospective cohort study

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Abstract

Background

Ovarian cancer is one of the most lethal cancers and women with type 2 diabetes (T2D) have even poorer survival from it. We assessed the prognosis of ovarian cancer in women with type 2 diabetes treated with metformin, other forms of antidiabetic medication, or statins.

Methods

Study cohort consisted of women with T2D diagnosed with ovarian cancer in Finland 1998–2011. They were identified from a nationwide diabetes database (FinDM), being linked to several national registers. Patients were grouped according to their medication in the three years preceding ovarian cancer diagnosis. The Aalen–Johansen estimator was used to describe cumulative mortality from ovarian cancer and from other causes in different medication groups. Mortality rates were analysed by Cox models, and adjusted hazard ratios (HR) with 95% confidence intervals (95% CIs) were estimated in relation to the use of different forms of medication. Main outcome measures were death from ovarian cancer and death from other causes.

Results

During the accrual period 421 newly diagnosed ovarian cancers were identified in the FinDM database. No evidence was found for any differences in mortality from ovarian cancer or other causes between different antidiabetic medication groups. Pre-diagnostic use of statins was observed to be associated with decreased mortality from ovarian cancer compared with no such use (HR 0.72, 95% CI 0.56–0.93).

Conclusions

Our findings are inconclusive as regards the association between metformin and ovarian cancer survival. However, some evidence was found for improved prognosis of ovarian cancer with pre-diagnostic statin use, requiring cautious interpretation, though.

Electronic supplementary material

The online version of this article (10.1186/s12885-018-4676-z) contains supplementary material, which is available to authorized users.

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Most cited references 40

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The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

Erik von Elm, Douglas G. Altman, Matthias Egger … (2008)

Much of biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

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Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.

K.G.M.M. Alberti, P.Z. Zimmet (1998)

The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.

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Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.

Jacques Ferlay, Hai-Rim Shin, Freddie Bray … (2010)

Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed. Copyright © 2010 UICC.

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Author and article information

Contributors

Elina Urpilainen: elina.urpilainen@gmail.com

Mikko Marttila: mikko@mikkomarttila.com

Ari Hautakoski: ari.hautakoski@gmail.com

Martti Arffman: martti.arffman@thl.fi

Reijo Sund: reijo.sund@helsinki.fi

Pirjo Ilanne-Parikka: pirjo.ilanne-parikka@diabetes.fi

Reetta Arima: reetta.arima@gmail.com

Jenni Kangaskokko: jenni.kangaskokko@coronaria.fi

Ulla Puistola: ulla.puistola@oulu.fi

Marianne Hinkula: Marianne.hinkula@oulu.fi

Esa Läärä: esa.laara@oulu.fi

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 28 July 2018

Publication date PMC-release: 28 July 2018

Publication date Collection: 2018

Volume: 18

Electronic Location Identifier: 767

Affiliations

[1 ]ISNI 0000 0004 4685 4917, GRID grid.412326.0, Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center Oulu, , University of Oulu and University Hospital of Oulu, ; P.O. Box 23, FIN-90029 Oulu, Finland

[2 ]ISNI 0000 0001 1013 0499, GRID grid.14758.3f, Children, Adolescents and Families Unit, Department of Welfare, National Institute for Health and Welfare, ; P.O. Box 310, FIN-90101 Oulu, Finland

[3 ]ISNI 0000 0001 0941 4873, GRID grid.10858.34, Research Unit of Mathematical Sciences, , University of Oulu, ; P.O. Box 8000, FIN-90014 Oulu, Finland

[4 ]ISNI 0000 0001 1013 0499, GRID grid.14758.3f, Service System Research Unit, , National Institute for Health and Welfare, ; P.O. Box 30, FIN-00271 Helsinki, Finland

[5 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, Centre for Research Methods, Department of Social Research, , University of Helsinki, ; Helsinki, Finland

[6 ]ISNI 0000 0001 0726 2490, GRID grid.9668.1, Institute of Clinical Medicine, , University of Eastern Finland, ; P.O. Box 1627, FIN-70211 Kuopio, Finland

[7 ]ISNI 0000 0004 0632 2975, GRID grid.478734.b, The Diabetes Center, Finnish Diabetes Association, ; FIN-33680 Tampere, Finland

[8 ]ISNI 0000 0001 0941 4873, GRID grid.10858.34, Medical Research Center Oulu, , University of Oulu, ; P.O. Box 8000, FIN-90014 Oulu, Finland

[9 ]Coronaria Diagnostics Oy, Oulu laboratory, FIN-90100 Oulu, Finland

Article

Publisher ID: 4676

DOI: 10.1186/s12885-018-4676-z

PMC ID: 6064082

PubMed ID: 30055585

SO-VID: 0b29455d-bf1a-4a6a-b8ee-e0736afbe65d

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 8 March 2018

Date accepted : 18 July 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004012, Jane ja Aatos Erkon Säätiö;

Award ID: T59127

Award Recipient : Reetta Arima

Funded by: The Cancer Foundation of Finland

Award ID: T59129

Award Recipient : Reetta Arima

Funded by: Finnish Government Research Funds

Award ID: K77729

Award Recipient : Elina Urpilainen

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: ovarian cancer,cancer survival,cancer prognosis,type 2 diabetes,metformin,statins,antidiabetic medication

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: ovarian cancer, cancer survival, cancer prognosis, type 2 diabetes, metformin, statins, antidiabetic medication

Prognosis of ovarian cancer in women with type 2 diabetes using metformin and other forms of antidiabetic medication or statins: a retrospective cohort study

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Abstract

Background

Methods

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Conclusions

Electronic supplementary material

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Karger: Oncology

Most cited references 40

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.

Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.

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