title: Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15): a potential screening tool for the prevention of colon cancer?
abstract: BACKGROUND
  Macrophage inhibitory cytokine-1 (MIC-1/GDF15) mediates nonsteroidal anti-inflammatory drug (NSAID) protection from colonic polyps in mice and is linked to the development of colorectal carcinoma in humans. Therefore, changes in serum MIC-1/GDF15 levels could predict the presence of premalignant colonic polyposis and assist in population screening strategies.
  
  
  METHODS
  Serum MIC-1/GDF15 levels were measured in subjects in the Polyp Prevention Trial, in which NSAID use and colon cancer risk factors were defined. Subjects had an initial adenoma removed, a repeat colonoscopy removing previously unidentified polyps, and serum MIC-1/GDF15 estimation. Three years later recurrent adenomas were identified and serum MIC-1/GDF15 levels reestimated. The relationship between serum MIC-1/GDF15 levels and adenoma presence or recurrence was examined.
  
  
  RESULTS
  Serum MIC-1/GDF15 levels differed by adenoma status and were significantly related to colon cancer risk factors. In addition, mean serum MIC-1/GDF15 levels rose with increasing numbers of adenomas present and high-risk adenoma recurrence. NSAID users had higher serum MIC-1/GDF15 concentrations, which were related to protection from adenoma recurrence. Furthermore, adjusted serum MIC-1/GDF15 levels at final follow-up were related to adenoma recurrence (highest quartile MIC-1/GDF15; OR = 14.7, 95% CI: 3.0-73).
  
  
  CONCLUSIONS
  These data suggest that MIC-1/GDF15 mediates at least some of the protection afforded by NSAIDs against human colonic polyposis. Furthermore, serum MIC-1/GDF15 levels vary with the development of adnenomatous colonic polyps.
  
  
  CONCLUSIONS
  Serum MIC-1/GDF15 determination may hold promise as the first serum screening test to assist the detection of premalignant adenomatous colonic polyposis.
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Victoria St, Sydney, NSW 2010, Australia. D.Brown@amr.org.au
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Hance
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Rogers
authors.forename: Leah B
authors.initials: LB
authors.lastname: Sansbury
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: Gwen
authors.initials: G
authors.lastname: Murphy
authors.forename: Adeyinka O
authors.initials: AO
authors.lastname: Laiyemo
authors.forename: Zhuoqiao
authors.initials: Z
authors.lastname: Wang
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Arthur
authors.initials: A
authors.lastname: Schatzkin
authors.forename: Mark
authors.initials: M
authors.lastname: Danta
authors.forename: Preeyaporn
authors.initials: P
authors.lastname: Srasuebkul
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
authors.forename: Elaine
authors.initials: E
authors.lastname: Lanza
mesh_terms: D000236:Adenoma / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D003111:Colonic Polyps / Q000097:blood / Q000517:prevention & control; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008297:Male; D008403:Mass Screening; D051379:Mice; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15