Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15): A potential screening tool for the prevention of colon cancer?

David A. Brown, Kenneth W. Hance, Connie J. Rogers, Leah B. Sansbury, Paul S. Albert, Gwen Murphy, Adeyinka O. Laiyemo, Zhuoqiao Wang, Amanda J. Cross, Arthur Schatzkin, Mark Danta, Preeyaporn Srasuebkul, Janaki Amin, Matthew Law, Samuel N. Breit, Elaine Lanza

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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. Impact: Serum MIC-1/GDF15 determination may hold promise as the first serum screening test to assist the detection of premalignant adenomatous colonic polyposis.

Original languageEnglish (US)
Pages (from-to)337-346
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number2
DOIs
StatePublished - Feb 2012

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

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    Brown, D. A., Hance, K. W., Rogers, C. J., Sansbury, L. B., Albert, P. S., Murphy, G., Laiyemo, A. O., Wang, Z., Cross, A. J., Schatzkin, A., Danta, M., Srasuebkul, P., Amin, J., Law, M., Breit, S. N., & Lanza, E. (2012). Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15): A potential screening tool for the prevention of colon cancer? Cancer Epidemiology Biomarkers and Prevention, 21(2), 337-346. https://doi.org/10.1158/1055-9965.EPI-11-0786