Study of Biochemical Markers to Determine the Acetylsalicylic Acid Chemopreventive Effect Through Antiplatelet Action

This study in healthy volunteers is the first step in developing a collaborative research program, which seeks to test the hypothesis that chemopreventive effect of acetylsalicylic acid (ASA) on colon cancer is due predominantly to its antiplatelet effect. The following features of the clinical evidence are consistent with the platelet-mediated hypothesis:

1. 1.The apparent saturability of the chemopreventive effect of ASA at low doses given once daily, found in long-term analyses of cardiovascular and adenoma recurrence randomized clinical trial, as well as in the vast majority of observational studies performed in different settings and with different methodology. A remarkably similar saturability of the cardioprotective effect of low dose ASA given once daily is explained by the irreversible nature of cyclooxygenase (COX)-1 inactivation in platelets, and limited capacity of human platelets for de novo protein synthesis.
2. 2.Given the short half-life of ASA in the human circulation (approximately 20 min) and the capacity of nucleated cells to resynthesize the acetylated COX-isozyme(s), it seems unlikely that a nucleated target could be suppressed throughout the 24-h dosing interval.
3. 3.One of the cardiovascular randomized clinical trial (Thrombosis Prevention Trial) in which the chemopreventive effect of ASA was detected on long-term follow-up, involved the administration of a controlled-release formulation of ASA (75 mg) with negligible systemic bioavailability.
4. 4.Enhanced platelet activation and thromboxane (TX)A2 generation in vivo has been demonstrated in patients with colorectal cancer and in Familial Adenomatous Polyposis patients.