Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

reposted from: Cancer Prev Res (Phila). 2012 February; 5(2): 164–178.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273592/

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Andrew T. Chan, Nadir Arber, John Burn, John Whay-Kuang Chia, Peter Elwood, Mark A. Hull,  Richard F. Logan, Peter M. Rothwell, Karsten Schrör, and John A. Baron

Abstract 

Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a = 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation.

The mechanism of action of aspirin for chemoprevention

Possible sites of action of aspirin in the prevention of colorectal cancer. COX-dependent and independent targets of aspirin are likely to be present in both epithelial and stromal cell compartments in colorectal adenomas and cancers. ATLs, aspirin-triggered lipoxins; COX, cyclooxygenase; PGE₂, prostaglandin E₂; S-1P, sphingosine-1-phosphate.