title: 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.
authors.affiliation: Carlos Sostres, Carla Jerusalen Gargallo, Angel Lanas, Department of Digestive Diseases, University Hospital Lozano Blesa, 50009 Zaragoza, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sostres
authors.affiliation: Carlos Sostres, Carla Jerusalen Gargallo, Angel Lanas, Department of Digestive Diseases, University Hospital Lozano Blesa, 50009 Zaragoza, Spain.
authors.forename: Carla Jerusalen
authors.initials: CJ
authors.lastname: Gargallo
authors.affiliation: Carlos Sostres, Carla Jerusalen Gargallo, Angel Lanas, Department of Digestive Diseases, University Hospital Lozano Blesa, 50009 Zaragoza, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
keywords: Aspirin; Benefits; Colorectal cancer; Cyclooxygenase inhibition; Mechanisms; Risk