The effect of aspirin and eicosapentaenoic acid on urinary biomarkers of prostaglandin E 2 synthesis and platelet activation in participants of the seAFOod polyp prevention trial

• Published in: International journal of cancer 2024-03, Vol.154 (5), p.873-885
• Main Authors: Sun, Ge, Fuller, Harriett, Fenton, Hayley, Race, Amanda D, Downing, Amy, Williams, Elizabeth A, Rees, Colin J, Brown, Louise C, Loadman, Paul M, Hull, Mark A
• Format: Article
• Language: English
• Subjects: Aspirin - pharmacology; Aspirin - therapeutic use; Biomarkers; Colonic Polyps; Eicosapentaenoic Acid; Humans; Platelet Activation; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Thromboxane B2 - urine
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.34764

Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation.