Non-Steroidal Anti-Inflammatory Drugs and Cancer Death in the Finnish Prostate Cancer Screening Trial

Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91–2.15) compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40–2.99, HR 1.91, 95% CI 1.57–2.32 and HR 1.93, 95% CI 1.58–2.37, respectively). The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05–1.18). When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65–0.73). Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70–0.82). Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded.

非甾体抗炎药（Non-steroidal Anti-inflammatory Drugs, NSAIDs），尤其是阿司匹林，已被证实与癌症发病率和死亡率降低存在关联。本研究针对芬兰前列腺癌筛查试验中的80144名男性，考察了总体癌症死亡率以及特定部位癌症的死亡风险。研究从国家药品报销数据库获取处方药使用信息，并通过问卷收集非处方药（over-the-counter）使用相关数据。采用Cox回归模型，计算了处方药与非处方药非甾体抗炎药使用情况下，总体及特定癌症死亡的风险比（Hazard Ratio, HR）与95%置信区间（Confidence Interval, CI）。在中位随访时长为15年的随访期间，共有7008名男性死于癌症。与未使用者相比，使用处方非甾体抗炎药的男性癌症死亡率显著升高（HR=2.02，95%CI：1.91–2.15）。具体而言，肺癌、结直肠癌及胰腺癌的死亡风险均有所增加，对应HR分别为2.68（95%CI：2.40–2.99）、1.91（95%CI：1.57–2.32）及1.93（95%CI：1.58–2.37）。竞争风险回归分析显示，该风险升高的结果依然成立（HR=1.11，95%CI：1.05–1.18）。若排除随访最后3年的用药情况，该效应出现反转（HR=0.69，95%CI：0.65–0.73）。使用处方或非处方阿司匹林并未降低癌症死亡率。但在联合处方药与非处方药阿司匹林的竞争风险回归分析中，其与总体癌症死亡率降低存在关联（HR=0.76，95%CI：0.70–0.82）。综上，非甾体抗炎药使用者的癌症死亡率升高，但排除随访最后3年的用药情况后，该风险不再显著存在。