School of Health Sciences, University of Tampere, Tampere, Finland.
Eur J Cancer. 2013 Mar;49(4):938-45. doi: 10.1016/j.ejca.2012.09.030. Epub 2012 Oct 15.
The cyclooxygenase 2 (COX-2) enzyme overexpression in prostate cancer has led to the hypothesis that COX-2 inhibition may reduce prostate cancer growth. Some previous studies have linked the usage of COX-2 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) with a decreased prostate cancer risk. We estimated the association between cumulative COX-2 inhibition by NSAID usage and prostate cancer risk at population level. All new prostate cancer cases in Finland during 1995-2002 and matched controls (24,657 case-control pairs) were identified from national registries. Detailed information on medication purchases was obtained from a national prescription database. A total cumulative COX-2 inhibition value was calculated based on total cumulative mg amount of each NSAID drug and the drug-specific COX-1/COX-2 inhibition ratio. Prostate cancer risk was analysed with propensity score-matched conditional logistic regression model. In total, 53.8% of the cases and 46.5% of the controls had any prescription-use of NSAIDs, while 8.1% and 7.9%, respectively, had used aspirin. Compared to the non-users, any NSAID use was associated with an elevated overall prostate cancer risk (46.4% versus 53.6%, respectively; odds ratio [OR] 1.3, 95% confidence interval [CI] 1.3, 1.4) and risk of advanced cancer (11.8% versus 14.1%; OR 1.6, 95% CI 1.5, 1.8). The risk remained elevated despite the amount of cumulative COX-2 inhibition. In a separate analysis, the risk increase was similar for each NSAID with the exception of aspirin, which was associated with a decreased overall prostate cancer risk (OR 0.90, 95% CI 0.84, 0.96) in a dose-dependent fashion. NSAID use is associated with an increased prostate cancer risk at the population level regardless of the COX-2 inhibition. This may be explained by systematic differences between prescription NSAID users and non-users. In contrast, aspirin use is associated with a decreased overall prostate cancer risk. Further studies on aspirin and prostate cancer will be needed.
环氧化酶 2（COX-2）在前列腺癌中的过度表达导致了 COX-2 抑制可能会降低前列腺癌生长的假说。一些先前的研究将 COX-2 抑制非甾体抗炎药（NSAIDs）的使用与前列腺癌风险降低联系起来。我们在人群水平上估计了 NSAIDs 使用导致的 COX-2 抑制累积与前列腺癌风险之间的关联。1995-2002 年期间芬兰所有新的前列腺癌病例（24657 对病例对照）均从国家登记处确定，并从国家处方数据库中获得了关于药物购买的详细信息。根据每种 NSAID 药物的总累积毫克数和药物特异性 COX-1/COX-2 抑制比计算出总累积 COX-2 抑制值。使用倾向评分匹配条件逻辑回归模型分析前列腺癌风险。总共，53.8%的病例和 46.5%的对照有任何 NSAIDs 处方使用，而分别有 8.1%和 7.9%的对照使用了阿司匹林。与非使用者相比，任何 NSAIDs 使用与前列腺癌总体风险升高相关（分别为 46.4%和 53.6%；优势比 [OR] 1.3，95%置信区间 [CI] 1.3，1.4）和晚期癌症风险（11.8%和 14.1%；OR 1.6，95%CI 1.5，1.8）。尽管 COX-2 抑制累积量不同，但风险仍然升高。在单独的分析中，除了阿司匹林之外，每种 NSAIDs 的风险增加情况相似，而阿司匹林与前列腺癌总体风险降低相关（OR 0.90，95%CI 0.84，0.96）呈剂量依赖性。无论 COX-2 抑制如何，NSAIDs 使用与人群中前列腺癌风险增加相关。这可能是由于处方 NSAIDs 使用者和非使用者之间存在系统性差异。相比之下，阿司匹林的使用与前列腺癌总体风险降低相关。需要进一步研究阿司匹林与前列腺癌之间的关系。
