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

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

Author information

  • 1Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
  • 2Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
  • 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
  • 4Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
  • 5Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
  • 6LabCorp, Raleigh, North Carolina, United States of America.
  • 7Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • 8Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.

Abstract

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:

ClinicalTrials.gov: WHS NCT00000479, MESA NCT00005487.

PMID:
27902713
PMCID:
PMC5130185
DOI:
10.1371/journal.pone.0165615
[PubMed - in process]
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