Antidiabetic Medication, Statins and the Risk and Prognosis of Non-endometrioid Endometrial Cancer in Women with Type 2 Diabetes

Reetta Arima; Mikko Marttila; Ari Hautakoski; Martti Arffman; Reijo Sund; Pirjo Ilanne-Parikka; Jenni Kangaskokko; Elina Urpilainen; Esa Läärä; Marianne Hinkula; Ulla Puistola

doi:10.21873/anticanres.12710

Antidiabetic Medication, Statins and the Risk and Prognosis of Non-endometrioid Endometrial Cancer in Women with Type 2 Diabetes

Anticancer Res. 2018 Jul;38(7):4169-4178. doi: 10.21873/anticanres.12710.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland reetta.arima@gmail.com.
² Children, Adolescents and Families Unit, Department of Welfare, National Institute for Health and Welfare, Oulu, Finland.
³ Research Unit of Mathematical Sciences, University of Oulu, Oulu, Finland.
⁴ Service System Research Unit, National Institute for Health and Welfare, Helsinki, Finland.
⁵ Centre for Research Methods, Department of Social Research, University of Helsinki, Helsinki, Finland.
⁶ Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁷ The Diabetes Center, Finnish Diabetes Association, Tampere, Finland.
⁸ Department of Pathology, Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland.
⁹ Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland.

PMID: 29970546
DOI: 10.21873/anticanres.12710

Abstract

Aim: To determine the incidence and prognosis of non-endometrioid endometrial cancer (EC) in relation to the use of metformin, other antidiabetic medication (ADM) and statins in patients with type 2 diabetes (T2D).

Materials and methods: In order to analyze the incidence and prognosis of non-endometrioid EC, two cohorts were obtained from a nationwide diabetes database (FinDM); 57 non-endometrioid ECs were observed in a cohort of 92,366 women with newly-diagnosed T2D during the follow-up (1996 to 2011) to assess the incidence, and a retrospective cohort of 105 women with T2D diagnosed with non-endometrioid EC (1998 to 2011) was used to estimate cumulative mortality from EC and other causes of death. Hazard ratios (HRs) with 95% confidence intervals (CIs) for EC incidence were estimated in the full-cohort analysis and in the nested case-control analysis, matched for age and duration of T2D. Cumulative mortality was estimated by using the Aalen-Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models regarding the pre-diagnostic use of different forms of ADM and statins.

Results: In the nested case-control analysis, the use of metformin was not associated with the risk of non-endometrioid EC (HR=1.09, 95% CI=0.59-2.00), whereas statin use was associated with a lower risk (HR=0.47, 95% CI=0.26-0.84). The results from the full-cohort analysis supported these findings. Mortality from non-endometrioid EC was not different between users of metformin and other types of oral ADM (HR=1.56, 95% CI=0.40-6.07) but was observed to be lower in statin users (HR=0.41, 95% CI=0.20-0.82).

Conclusion: Our findings were inconclusive regarding the association of metformin with the risk and prognosis of non-endometrioid EC. However, statin use was associated with a lower incidence and mortality from this disease.

Keywords: Endometrial cancer; case–control; cohort; metformin; non-endometrioid; prognosis; statins.

MeSH terms

Adult
Aged
Case-Control Studies
Cohort Studies
Diabetes Mellitus, Type 2 / drug therapy*
Endometrial Neoplasms / epidemiology*
Female
Humans
Hypoglycemic Agents / therapeutic use*
Incidence
Metformin / therapeutic use*
Middle Aged
Prognosis
Retrospective Studies
Risk

Substances

Hypoglycemic Agents
Metformin