Plasma lipoxin A(4) and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas

• Type of Material: Article
• Authors: Veronika Fedirko, Emory University; Gail McKeown-Eyssen, University of Toronto; Charles N. Serhan, Brigham and Women’s Hospital and Harvard Medical School; Elizabeth L. Barry, Geisel School of Medicine at Dartmouth; Robert S. Sandler, University of North Carolina; Jane C. Figueiredo, University of Southern California; Dennis J. Ahnen, Department of Veterans Affairs Medical Center; Robert S. Bresalier, University of Texas M.D. Anderson Cancer Center; Douglas J. Robertson, Department of Veterans Affairs Medical Center; Carlton W. Anderson, University of North Carolina; John A. Baron, University of North Carolina
• Language: English
• Date: 2017-08-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/mc.22629
• Title of Journal or Parent Work: Molecular Carcinogenesis
• ISSN: 0899-1987
• Volume: 56
• Issue: 8
• Start Page: 1977
• End Page: 1983
• Grant/Funding Information: Use of the Dartmouth Biospecimen Storage Facility was supported by the Center for Molecular Epidemiology COBRE program with a grant from the National Institute of General Medical Sciences (P20 GM104416).; This study was funded by the US Public Health Service grant CA059005 (PI: J.A. Baron).; This research was also supported by the National Institutes of Health P30 DK34987 (PI: R.S. Sandler) and R37 GM038765-30 (PI: C.N. Serhan).
• Keywords: aspirin; INFLAMMATION; lipoxin A(4); GROWTH; LIPID MEDIATORS; Oncology; colorectal neoplasms; Science & Technology; ANALOG SUPPRESS; Life Sciences & Biomedicine; COLORECTAL ADENOMAS; randomized controlled trial; resolvin D1; CELL-PROLIFERATION; OMEGA-3-FATTY-ACIDS; PROGRESSION; Biochemistry & Molecular Biology; RESOLUTION; CANCER
• Research Categories: Health Sciences, Public Health; Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology

Abstract

Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4(LXA4) and resolvin D1(RvD1)] with risk for recurrent adenoma. In this pilot study, we used data and biosamples from an adenoma chemoprevention study investigating the effects of aspirin and/or folic acid on the occurrence of colorectal adenomas. In the parent study, 1121 participants with a recent adenoma were randomized to study agents to be taken until the next surveillance colonoscopy about 3 years later. In this pilot study, LXA4and RvD1 from samples taken near the end of study treatment were measured in a randomly selected sub-set of 200 participants. Commercially available ELISA kits to assay the analytes were validated using a metabololipidomic LC-MS/MS assay. Poisson regression with a robust error variance was used to calculate risk ratios and 95% confidence intervals. Plasma LXA4and RvD1 were not associated with the risk of adenoma occurrence. LXA4at the end of study follow-up was 32% (P = 0.01) proportionately higher in women compared to men. A similar non-significant trend toward higher levels among women was observed for RvD1. Our preliminary findings provided no evidence that plasma LXA4or RvD1 are associated with reduced risk of colorectal adenoma occurrence, but suggest LXA4may differ among men and women. Future studies focusing on SPM's local effects and levels in the colon are needed.