Stroke Prevention Research Unit, University Department of Clinical Neurology, University of Oxford, Oxford, UK.
Lancet Oncol. 2012 May;13(5):518-27. doi: 10.1016/S1470-2045(12)70112-2. Epub 2012 Mar 21.
Long-term follow-up of randomised trials of aspirin in prevention of vascular events showed that daily aspirin reduced the incidence of colorectal cancer and several other cancers and reduced metastasis. However, statistical power was inadequate to establish effects on less common cancers and on cancers in women. Observational studies could provide this information if results can be shown to be reliable. We therefore compared effects of aspirin on risk and outcome of cancer in observational studies versus randomised trials.
For this systematic review, we searched for case-control and cohort studies published from 1950 to 2011 that reported associations between aspirin use and risk or outcome of cancer. Associations were pooled across studies by meta-analysis and stratified by duration, dose, and frequency of aspirin use and by stage of cancer. We compared associations from observational studies with the effect of aspirin on 20-year risk of cancer death and on metastasis in the recent reports of randomised trials.
In case-control studies, regular use of aspirin was associated with reduced risk of colorectal cancer (pooled odds ratio [OR] 0·62, 95% CI 0·58-0·67, p(sig)<0·0001, 17 studies), with little heterogeneity (p(het)=0·13) in effect between studies, and good agreement with the effect of daily aspirin use on 20-year risk of death due to colorectal cancer from the randomised trials (OR 0·58, 95% CI 0·44-0·78, p(sig)=0·0002, p(het)=0·45). Similarly consistent reductions were seen in risks of oesophageal, gastric, biliary, and breast cancer. Overall, estimates of effect of aspirin on individual cancers in case-control studies were highly correlated with those in randomised trials (r(2)=0·71, p=0·0006), with largest effects on risk of gastrointestinal cancers (case-control studies, OR 0·62, 95% CI 0·55-0·70, p<0·0001, 41 studies; randomised trials, OR 0·54, 95% CI 0·42-0·70, p<0·0001). Estimates of effects in cohort studies were similar when analyses were stratified by frequency and duration of aspirin use, were based on updated assessments of use during follow-up, and were appropriately adjusted for baseline characteristics. Although fewer observational studies stratified analyses by the stage of cancer at diagnosis, regular use of aspirin was associated with a reduced proportion of cancers with distant metastasis (OR 0·69, 95% CI 0·57-0·83, p(sig)<0·0001, p(het)=0·89, five studies), but not with any reduction in regional spread (OR 0·98, 95% CI 0·88-1·09, p(sig)=0·71, p(het)=0·88, seven studies), consistent again with the findings in randomised trials.
Observational studies show that regular use of aspirin reduces the long-term risk of several cancers and the risk of distant metastasis. Results of methodologically rigorous studies are consistent with those obtained from randomised controlled trials, but sensitivity is particularly dependent on appropriately detailed recording and analysis of aspirin use.
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长期随访的阿司匹林预防血管事件的随机试验表明，每天使用阿司匹林可降低结直肠癌和其他几种癌症的发生率，并减少转移。然而，统计效力不足以确定对不太常见的癌症和女性癌症的影响。如果结果被证明是可靠的，观察性研究可以提供这些信息。因此，我们比较了观察性研究和随机试验中阿司匹林对癌症风险和结果的影响。
为了进行这项系统评价，我们从 1950 年到 2011 年搜索了报道阿司匹林使用与癌症风险或结果之间关联的病例对照和队列研究。通过荟萃分析，对来自研究的关联进行了汇总，并按阿司匹林使用的持续时间、剂量和频率以及癌症的阶段进行了分层。我们将观察性研究的关联与随机试验最近报告的阿司匹林对 20 年癌症死亡风险和转移的影响进行了比较。
在病例对照研究中，规律使用阿司匹林与结直肠癌风险降低相关（汇总比值比 [OR]0.62，95%CI0.58-0.67，p(sig)<0.0001，17 项研究），研究之间的效应差异不大（p(het)=0.13），与随机试验中阿司匹林每日使用对结直肠癌 20 年死亡风险的影响一致（OR0.58，95%CI0.44-0.78，p(sig)=0.0002，p(het)=0.45）。同样一致的是，食管、胃、胆道和乳腺癌的风险也有所降低。总体而言，病例对照研究中阿司匹林对个别癌症的效应估计与随机试验非常相关（r(2)=0.71，p=0.0006），对胃肠道癌症的风险影响最大（病例对照研究，OR0.62，95%CI0.55-0.70，p<0.0001，41 项研究；随机试验，OR0.54，95%CI0.42-0.70，p<0.0001）。当根据阿司匹林使用的频率和持续时间对队列研究进行分层分析时，估计的效果相似，并且基于随访期间使用情况的最新评估，并且适当调整了基线特征。尽管对观察性研究分层分析的癌症分期的研究较少，但规律使用阿司匹林与远处转移的癌症比例降低相关（OR0.69，95%CI0.57-0.83，p(sig)<0.0001，p(het)=0.89，五项研究），但与局部扩散无任何减少相关（OR0.98，95%CI0.88-1.09，p(sig)=0.71，p(het)=0.88，七项研究），这与随机试验的结果一致。
观察性研究表明，规律使用阿司匹林可降低多种癌症的长期风险和远处转移的风险。方法学严格的研究结果与随机对照试验的结果一致，但敏感性特别依赖于对阿司匹林使用情况的详细记录和分析。
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