Aspirin and cancer preventionBMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e2480 (Published 03 April 2012) Cite this as: BMJ 2012;344:e2480
- Tobias Kurth, director of research1
When Eichengrün and colleagues at dye manufacturer Friedrich Bayer & Co synthesised acetylsalicylic acid in 1897 the success story of aspirin began,1 and its potential applications are still being revealed. It is well established that aspirin reduces pain, limits the inflammatory response, and reduces cardiovascular disease but that it can lead to major bleeding events and gastrointestinal upset. For several years increasing numbers of studies have suggested a benefit of aspirin on the occurrence of polyps and colorectal cancer.2 3 Potential beneficial effects on other common cancer types have also been reported.4 Two recently published large scale studies have provided additional evidence that low dose aspirin reduces the incidence of cancer, death from cancer, and cancer metastasis.5 6
The first, an analysis of the short term effects of daily aspirin (<300 mg) use on various cancer related outcomes in 51 randomised controlled trials,5 found that allocation to aspirin reduced deaths from cancer (odds ratio 0.85, 95% confidence interval 0.76 to 0.96), particularly from five years of daily use onwards, resulting in fewer deaths from non-vascular disease. In addition, aspirin significantly reduced the risk of incident cancer in women and men by about 25%. Furthermore, the effect of low dose aspirin on incident cancer increased with longer follow-up, whereas its effects on major cardiovascular disease and extracranial bleeds decreased.
The second study summarised the effects of aspirin on cancer metastasis in five large scale randomised trials.6 In this study, allocation to aspirin reduced the risk of cancer with distant metastasis. The hazard ratio was 0.64 (0.48 to 0.84) for all cancers, 0.54 (0.38 to 0.77) for adenocarcinoma, and 0.82 (0.53 to 1.28) for other solid cancers. The study’s findings suggest that low dose aspirin should be considered in the treatment of some patients with cancer.
The findings of the two recent studies are compelling and strongly suggest that, at least for specific subgroups, daily low dose aspirin could reduce cancer related outcomes. However, can we now argue that everyone should take a daily aspirin? Should we conclude that because daily aspirin has confirmed benefits on cardiovascular disease and now seems to be effective in preventing cancer, two of the major contributors to mortality and morbidity in the general population, we should be more proactive in getting people to take daily aspirin?
Despite clear results from the two recent analyses, the topic is still complex and many uncertainties remain.7 The two studies include evidence from randomised controlled trials. Although well conducted randomised trials are considered to provide strong clinical evidence, trial participants are a highly selected group, recruited according to clear inclusion and exclusion criteria, and evidence from trials cannot always be extrapolated and applied to the general population. Although these recent results are supported by some observational studies,3 7 the scientific question of whether we should recommend low dose aspirin for everyone could be answered only by using a distinct causal modelling approach. Such an approach is complex and has rarely been used to analyse observational data.8 If low dose aspirin has a causal effect in cancer prevention, then this effect must be present across different study designs. However, large scale primary prevention trials in men and women have failed to show an effect of low dose aspirin on colorectal cancer, total cancer, or cancer mortality.9 10
There is little doubt that low dose aspirin has beneficial effects on cardiovascular events. But even in this area, which has a large body of evidence,11 it is unclear which patients should be given aspirin because the benefits are not constant across groups with different risk factor profiles.12 For cancer prevention, where far less published evidence is available, the uncertainty is even greater. For example, what should a doctor recommend to a patient with Barrett’s oesophagus, who is considered to be at higher risk of developing cancer, but who may not tolerate the gastric side effects of aspirin. What about patients with asthma? How should a doctor advise the patient with a family history of cancer but a propensity to bleed in whom there is a small chance that aspirin may induce a major bleeding event? Results of one of the recent studies suggest that an increased risk of bleeding is only apparent in the short term,5 but should we take the risk of prescribing aspirin in the hope that the patient gets through that short time window of increased bleeding risk without an adverse event?
Too many questions remain unanswered to warrant a recommendation to treat all adults with low dose aspirin to prevent cancer. However, the increasing evidence that aspirin may interfere with the pathogenesis of at least some cancers is compelling and should motivate further targeted research at the population level. Efforts to study the effect of low dose aspirin on cancer occurrence should include the application of appropriate causal modelling to observational data, in addition to the identification of subgroups of patients who would benefit most and those in whom adverse effects of aspirin are most likely to occur. Research should focus on plausible interactions of specific biological mechanisms, including biomarkers and genetic information. Until then, doctors should continue to make decisions on long term treatment with low dose aspirin in individual patients by carefully balancing risks and benefits.
Cite this as: BMJ 2012;344:e2480
Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; TK is consulting clinical epidemiology editor of the BMJ.
Provenance and peer review: Commissioned; not externally peer reviewed.