OBJECTIVES The aim of this study was to investigate the associations of aspirin, metformin, and statins with lung cancer risk and mortality using population-based nationwide cohort data. METHODS This study included a total of 732,199 participants who had undergone a national health check-up in 2002-2003. Lung cancer incidence and mortality were identified using a registered lung cancer diagnosis code (ICD-10 code C34) and the Korean National Death Registry. The study participants were followed from January 1, 2004 to 31 December 2013. Medication exposure was defined by cumulative duration of use and cumulative defined daily dose (cDDD) per 2-year interval. To avoid immortal time bias, drug exposure was inserted as a time-dependent variable in Cox analysis, which evaluated the associations of these medications with lung cancer. RESULTS Metformin use had protective association with lung cancer incidence (P's-for-trend = 0.008) and mortality (P's-for-trend <0.001) in a dose-response fashion, and these associations were prominent among participants with cDDD of metformin ≥ 547.5, compared with non-diabetic patients. Lung cancer mortality was dose-dependently reduced with the use of aspirin ([P's-for-trends 0.046] and statin [P's-for-trends <0.001]). Combined use of aspirin, statins and metformin showed more prominent protective associations with lung cancer risk and mortality. CONCLUSION Use of aspirin, metformin, and statins had independent protective associations with lung cancer mortality, and metformin had inverse association with lung cancer risk. Further studies are necessary to develop clinically applicable anticancer strategies of these drugs for the reduction of lung cancer and related mortality.

中文翻译：

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阿司匹林、他汀类药物和二甲双胍与肺癌风险和相关死亡率的关联：基于人群的全国代表性数据的时间依赖性分析

目的 本研究的目的是使用基于人群的全国队列数据调查阿司匹林、二甲双胍和他汀类药物与肺癌风险和死亡率的关联。方法 本研究共纳入 732,199 名在 2002-2003 年接受过全国健康检查的参与者。使用注册的肺癌诊断代码（ICD-10 代码 C34）和韩国国家死亡登记处确定肺癌的发病率和死亡率。研究参与者的随访时间为 2004 年 1 月 1 日至 2013 年 12 月 31 日。药物暴露由累积使用持续时间和每 2 年间隔的累积限定日剂量 (cDDD) 定义。为了避免不朽的时间偏差，在 Cox 分析中插入了药物暴露作为时间相关变量，该分析评估了这些药物与肺癌的关联。结果 使用二甲双胍与肺癌发病率（趋势 P = 0.008）和死亡率（趋势 P <0.001）呈剂量反应关系，这些相关性在二甲双胍 cDDD ≥ 547.5 的参与者中尤为突出，与非糖尿病患者相比。使用阿司匹林（[P's-for-trends 0.046] 和他汀类 [P's-for-trends <0.001]），肺癌死亡率呈剂量依赖性降低。阿司匹林、他汀类药物和二甲双胍的联合使用显示出与肺癌风险和死亡率更显着的保护关联。结论 阿司匹林、二甲双胍和他汀类药物的使用与肺癌死亡率具有独立的保护性关联，而二甲双胍与肺癌风险呈负相关。