Effect of Low-dose and Standard-dose Aspirin on PGE2 Biosynthesis Among Individuals with Colorectal Adenomas: A Randomized Clinical Trial
| Autor: | John J. Garber, James M. Richter, David A. Drew, Manish Gala, Marina V. Magicheva-Gupta, Madeline M. Schuck, Dylan C. Zerjav, Patrick Miller, Joseph C. Yarze, Francis Colizzo, Hamed Khalili, Kyle Staller, Peter J. Carolan, Ginger L. Milne, Andrew T. Chan, Oliver Takacsi-Nagy, Norman S. Nishioka, Katheleen O. Stewart, Giovanna Petrucci, Wenjie Ma, Carlo Patrono, Samantha M. Chin, Amit Joshi, Lawrence R. Zukerberg, Dana Meixell, Daniel C. Chung, Jennifer Mackinnon Krems, Katherine K. Gilpin, Melanie P. Parziale, Emily N. Pond, Molin Wang, Bianca Rocca |
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| Rok vydání: | 2020 |
| Předmět: |
Adenoma
Adult Male 0301 basic medicine Cancer Research medicine.medical_specialty Adolescent Settore BIO/14 - FARMACOLOGIA aspirin Colorectal cancer Urinary system Urine platelet aspirin colon cancer thromboxane pge1 Gastroenterology Article Dinoprostone law.invention Excretion Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Double-Blind Method Randomized controlled trial law Internal medicine Humans Medicine Aged Aged 80 and over platelet Creatinine Aspirin business.industry Anti-Inflammatory Agents Non-Steroidal pge1 Middle Aged medicine.disease 030104 developmental biology colon cancer Oncology chemistry 030220 oncology & carcinogenesis Female Colorectal Neoplasms business thromboxane medicine.drug |
| Zdroj: | Cancer Prev Res (Phila) |
| ISSN: | 1940-6215 1940-6207 |
| DOI: | 10.1158/1940-6207.capr-20-0216 |
| Popis: | Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8–12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (−4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (−15%; P = 0.018) or 325 mg/day (−28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769. |
| Databáze: | OpenAIRE |
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