• Prévention

  • Chimioprévention

  • Colon-rectum

Plasma Metabolomics Analysis of Aspirin Treatment and Risk of Colorectal Adenomas

Menée à l'aide d'une chromatographie en phase liquide couplée à la spectroscopie de masse et d'échantillons plasmatiques collectés entre 1994 et 2001 auprès de 523 participants inclus dans un essai randomisé, cette étude analyse le mécanisme métabolomique associé à l'effet de l'aspirine dans la chimioprévention du cancer colorectal

Despite substantial observational and experimental evidence that aspirin use can provide protection against the development of colorectal neoplasia, our understanding of the molecular mechanisms involved is inadequate and limits our ability to use this drug effectively and safely for chemoprevention. We employed an untargeted plasma metabolomics approach using liquid chromatography with high-resolution mass spectroscopy to explore novel metabolites that may contribute to the chemopreventive effects of aspirin. Associations between levels of metabolic features in plasma and aspirin treatment were investigated among 523 participants in a randomized placebo-controlled clinical trial of two doses of aspirin (81 or 325 mg/day) and were linked to risk of colorectal adenoma occurrence over 3 years of follow-up. Metabolic pathways that were altered with aspirin treatment included linoleate and glycerophospholipid metabolism for the 81 mg dose and carnitine shuttle for both doses. Metabolites whose levels increased with 81 mg/day aspirin treatment and were also associated with decreased risk of adenomas during follow-up included certain forms of lysophosphotidylcholine (LysoPC) and lysophosphotidylethanolamine (LysoPE) as well as trihydroxyoctadecenoic acid (TriHOME), which is a derivative of linoleic acid and is upstream of cyclooxygenase inhibition by aspirin in the linoleate and arachidonic acid metabolism pathways. In conclusion, our findings regarding lysophospholipids and metabolites in the linoleate metabolism pathway may provide novel insights into the chemopreventive effects of aspirin in the colorectum, although they should be considered hypothesis-generating at this time.

Cancer Prevention Research

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