Lacroix Olivia, Couttenier Alexandra, Vaes Evelien, Cardwell Chris R, De Schutter Harlinde, Robert Annie
Université catholique de Louvain, Institut de recherche expérimentale et clinique, Pôle d'épidémiologie et de biostatistique, Bruxelles, Belgium.
Université catholique de Louvain, Institut de recherche expérimentale et clinique, Pôle d'épidémiologie et de biostatistique, Bruxelles, Belgium.
Cancer Epidemiol. 2018 Apr;53:149-155. doi: 10.1016/j.canep.2018.02.001. Epub 2018 Feb 22.
Preclinical studies have shown anticancer activities of metformin in gastric cancer and a recent epidemiological study showed a decrease in recurrence and mortality of gastric cancer in metformin users. This study aimed to assess the impact of metformin on gastric cancer survival in diabetic patients at a Belgian population level.
We conducted an observational, population-based study by linking data of the Belgian Cancer Registry with medical claims data coming from the health insurance companies for patients diagnosed with stage I to III gastric adenocarcinoma between 2006 and 2012. Information on gastric cancer-specific deaths was retrieved from mortality records collected by regional governments. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) and cancer-specific mortality (CSS).
In our population of 371 patients, a reduction in all-cause mortality was observed in metformin users (adjusted HR = 0.73, 95% CI: [0.52; 1.01], p = 0.06) but not for cancer specific mortality (adjusted HR = 0.86, 95% CI: [0.56; 1.33], p = 0.50). Pre-diagnosis exposure to metformin was associated with a significant improvement in OS (adjusted HR = 0.75, 95% CI: [0.57; 0.98], p = 0.04) that was not significant for CSS (adjusted HR = 0.89, 95% CI: [0.62; 1.28], p = 0.52). Moreover, no dose-response relationship between metformin use and either all-cause or cancer-specific mortality was observed.
In the first population based study of metformin use in gastric cancer adenocarcinoma patients with previous diabetes, our findings suggest that metformin use might improve overall mortality. However, no such association was found for cancer-specific survival. Additional studies in other populations are required.
临床前研究已表明二甲双胍在胃癌中具有抗癌活性，并且最近一项流行病学研究显示，使用二甲双胍的患者胃癌复发率和死亡率有所降低。本研究旨在评估在比利时人群水平上，二甲双胍对糖尿病患者胃癌生存率的影响。
我们通过将比利时癌症登记处的数据与来自健康保险公司的医疗理赔数据相链接，开展了一项基于人群的观察性研究，这些医疗理赔数据涉及2006年至2012年间被诊断为I至III期胃腺癌的患者。胃癌特异性死亡信息是从地区政府收集的死亡记录中获取的。采用时间依赖性Cox回归模型计算总生存期（OS）和癌症特异性死亡率（CSS）的风险比（HRs）及95%置信区间（CI）。
在我们的371例患者群体中，观察到使用二甲双胍的患者全因死亡率有所降低（校正HR = 0.73，95% CI：[0.52; 1.01]，p = 0.06），但癌症特异性死亡率未降低（校正HR = 0.86，95% CI：[0.56; 1.33]，p = 0.50）。诊断前接触二甲双胍与OS的显著改善相关（校正HR = 0.75，95% CI：[0.57; 0.98]，p = 0.04），但对CSS而言不显著（校正HR = 0.89，95% CI：[0.62; 1.28]，p = 0.52）。此外，未观察到二甲双胍使用与全因或癌症特异性死亡率之间存在剂量反应关系。
在第一项针对既往患有糖尿病的胃腺癌患者使用二甲双胍的基于人群的研究中，我们的研究结果表明，使用二甲双胍可能会改善总死亡率。然而，未发现其与癌症特异性生存率存在此类关联。需要在其他人群中开展进一步研究。
