Association of N-Linked Glycoprotein Acetyls and Colorectal Cancer Incidence and Mortality

PLoS One. 2016 Nov 30;11(11):e0165615. doi: 10.1371/journal.pone.0165615. eCollection 2016.


Background: Acute phase proteins highlight the dynamic interaction between inflammation and oncogenesis. GlycA, a novel nuclear magnetic resonance (NMR) inflammatory marker that identifies primarily circulating N-acetyl glycan groups attached to acute phase proteins, may be a future CRC risk biomarker.

Methods: We examined the association between GlycA and incident CRC and mortality in two prospective cohorts (N = 34,320); Discovery cohort: 27,495 participants from Women's Health Study (WHS); Replication cohort: 6,784 participants from Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable Cox models were adjusted for clinical risk factors and compared GlycA to acute phase proteins (high-sensitivity C-reactive protein [hsCRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]).

Results: In WHS (median follow-up 19 years, 337 cases, 103 deaths), adjusted HRs (95% CIs) per SD increment of GlycA for CRC incidence and mortality were 1.19 (1.06-1.35; p = 0.004) and 1.24 (1.00-1.55; p = 0.05), respectively. We replicated findings in MESA (median follow-up 11 years, 70 cases, 23 deaths); HRs (95% CIs) per SD of GlycA for CRC incidence and mortality were 1.32 (1.06-1.65; p = 0.01) and 1.54 (1.06-2.23; p = 0.02), respectively, adjusting for age, sex, and race. Pooled analysis, adjusted HR (95% CI) per SD of GlycA for CRC incidence and mortality was 1.26 (1.15-1.39; p = 1 x 10-6). Other acute phase proteins (hsCRP, fibrinogen, and sICAM-1) had weaker or no association with CRC incidence, while only fibrinogen and GlycA were associated with CRC mortality.

Conclusions: The clinical utility of GlycA to personalize CRC therapies or prevention warrants further study.

Trial registration: WHS NCT00000479, MESA NCT00005487.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute-Phase Proteins / analysis
  • Aged
  • Biomarkers / blood*
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / mortality*
  • Female
  • Follow-Up Studies
  • Glycoproteins / blood*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Polysaccharides / blood*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Survival Rate
  • United States / epidemiology


  • Acute-Phase Proteins
  • Biomarkers
  • Glycoproteins
  • Polysaccharides
  • C-Reactive Protein

Associated data