Aspirin, cyclooxygenase inhibition and colorectal cancer

Abstract

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

Keywords: Aspirin, Colorectal cancer, Cyclooxygenase inhibition, Mechanisms, Risk, Benefits

Core tip: Colorectal cancer (CRC) is a major cause of morbidity and mortality worldwide. Currently, CRC screening programs are not widely available and need to be improved. New prevention strategies are therefore necessary. Daily low-dose aspirin, as given for the prevention of cardiovascular disease events, has demonstrated benefits in clinical and basic studies in terms of preventing adenoma recurrence and decreasing the incidence of CRC and attributable mortality. These findings indicate that the antiplatelet action of aspirin plays a central role in its antitumor effect. Cyclooxygenase-dependent and independent mechanisms have been suggested to explain this effect. Extensive translational medical research is mandatory for future progress in CRC prevention.