title: Plasma lipoxin A4and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas.
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.
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Veronika
authors.identifier: 0000-0002-7805-9913
authors.initials: V
authors.lastname: Fedirko
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gail
authors.initials: G
authors.lastname: McKeown-Eyssen
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital & Harvard Medical School, Center for Experimental Therapeutics and Reperfusion Injury, Boston, Massachusetts.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Barry
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.affiliation: Department of Preventive Medicine, Keck School Of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.affiliation: Department of Veterans Affairs Medical Center, Denver, Colorado.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Ahnen
authors.affiliation: Department of Gastrointestinal Medicine and Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bresalier
authors.affiliation: Department of Veterans Affairs Medical Center, White River Junction VT and The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Medical School, Lebanon, New Hampshire.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Robertson
authors.affiliation: Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Carlton W
authors.initials: CW
authors.lastname: Anderson
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
mesh_terms: D000236:Adenoma / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000097:blood*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D044045:Lipoxins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012007:Rectum / Q000187:drug effects; D012306:Risk; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; C040527:lipoxin A4; C518399:resolvin D1; D014803:Vitamin B Complex; D004281:Docosahexaenoic Acids; D005492:Folic Acid; D001241:Aspirin
keywords: aspirin; colorectal neoplasms; lipoxin A4; randomized controlled trial; resolvin D1