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The role of aspirin in cancer prevention

Abstract

Clinical guidelines for prophylactic aspirin use currently only consider the cardiovascular benefits of aspirin, weighed against the potential harm from aspirin-induced bleeding. Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, but in average-risk populations, these benefits alone do not outweigh harms from aspirin-induced bleeding. Recently published secondary analyses of cardiovascular trials provide the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75–100 mg daily). This Review considers the general mechanism of action that defines aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) as a class, the specific advantages of aspirin over other NSAIDs for prophylactic use, the current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activation may mediate both the cardioprotective and cancer-preventive effects of low-dose aspirin. It also considers how even a 10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favourably in average-risk populations.

Key Points

  • Clinical guidelines for prophylactic aspirin use currently only consider the cardiovascular benefits of aspirin, weighed against the potential harm from aspirin-induced bleeding

  • Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer but in average-risk populations this benefit alone does not outweigh harm from aspirin-induced bleeding

  • Secondary analyses of cardiovascular trials showed that daily low-dose aspirin use may also reduce the incidence of all cancers combined, although uncertainty remains about the magnitude of the potential benefit.

  • Even a 10% reduction in overall cancer incidence could substantially broaden the indications for prophylactic daily treatment with low-dose aspirin

  • As daily treatment with low-dose aspirin was as effective as treatment with higher doses, inhibition of platelet activation may mediate both the cardioprotective and cancer preventive effects of low-dose aspirin

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Figure 1: Mechanism of action of high-dose and low-dose aspirin depicted on a simplified schematic of the cyclooxygenase pathway.
Figure 2: Hypothesized mechanism by which the inhibition of COX-1 in platelets by low-dose aspirin may suppress the induction of COX-2 in adjacent nucleated cells of the intestinal mucosa in early stage neoplasia.
Figure 3: 5-year risk of vascular events and major bleeding based on primary prevention trials of aspirin and placebo and hypothetical 10% reduction in cancer incidence by age and sex.

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Acknowledgements

The authors wish to acknowledge the help of Brian Carter in constructing the analyses of cumulative risk in the risk–benefit analyses and Robin Nilson for assistance in the literature search and reference editing.

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All authors contributed to researching data for the article, and to writing, editing and reviewing the manuscript before submission.

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Correspondence to Michael J. Thun.

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C. Patrono is a consultant for and receives honoraria from AstraZeneca; he is a consultant for, and receives honoraria and grant support from Bayer; he receives honoraria from Eli Lilly; he is a consultant for Merck, Novartis, NicOx, Sanofi-Aventis and Servier; and he also receives grant support from Servier. The other authors declare no competing interests.

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Thun, M., Jacobs, E. & Patrono, C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol 9, 259–267 (2012). https://doi.org/10.1038/nrclinonc.2011.199

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