Arima Reetta, Marttila Mikko, Hautakoski Ari, Arffman Martti, Sund Reijo, Ilanne-Parikka Pirjo, Kangaskokko Jenni, Urpilainen Elina, Läärä Esa, Hinkula Marianne, Puistola Ulla
Department of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland
Children, Adolescents and Families Unit, Department of Welfare, National Institute for Health and Welfare, Oulu, Finland.
Anticancer Res. 2018 Jul;38(7):4169-4178. doi: 10.21873/anticanres.12710.
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).
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.
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).
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.
确定2型糖尿病（T2D）患者中，使用二甲双胍、其他抗糖尿病药物（ADM）和他汀类药物与非子宫内膜样子宫内膜癌（EC）的发病率及预后之间的关系。
为分析非子宫内膜样EC的发病率及预后，从全国糖尿病数据库（FinDM）中获取了两个队列；在随访期间（1996年至2011年），对92366例新诊断为T2D的女性队列进行观察，其中有57例非子宫内膜样EC，以评估发病率，同时使用一个回顾性队列，该队列包含105例诊断为非子宫内膜样EC的T2D女性（1998年至2011年），用于估计EC及其他死因的累积死亡率。在全队列分析和巢式病例对照分析中，对EC发病率的风险比（HR）及95%置信区间（CI）进行估计，并根据年龄和T2D病程进行匹配。使用Aalen-Johansen估计器估计累积死亡率。通过Cox模型分析不同形式的ADM和他汀类药物诊断前使用情况的特定病因死亡率。
在巢式病例对照分析中，使用二甲双胍与非子宫内膜样EC风险无关（HR = 1.09，95% CI = 0.59 - 2.00），而使用他汀类药物与较低风险相关（HR = 0.47，95% CI = 0.26 - 0.84）。全队列分析结果支持这些发现。二甲双胍使用者与其他类型口服ADM使用者的非子宫内膜样EC死亡率无差异（HR = 1.56，95% CI = 0.40 - 6.07），但他汀类药物使用者的死亡率较低（HR = 0.41，95% CI = 0.20 - 0.82）。
关于二甲双胍与非子宫内膜样EC风险及预后之间的关联，我们的研究结果尚无定论。然而，使用他汀类药物与该疾病较低的发病率和死亡率相关。
