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

Abstract

BackgroundAcute 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.MethodsWe 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]).ResultsIn 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.ConclusionsThe clinical utility of GlycA to personalize CRC therapies or prevention warrants further study.Trial RegistrationClinicalTrials.gov: WHS NCT00000479, MESA NCT00005487

Associations of ideal cardiovascular health with GlycA, a novel inflammatory marker: The Multi‐Ethnic Study of Atherosclerosis

“…Despite its recent characterization, GlycA is becoming increasingly recognized as an important prognostic marker for CVD, diabetes, cancer, and mortality risk 8,[10][11][12][13] ; however the best interventions to reduce GlycA are not established. For example, although statin therapy has been shown to reduce hsCRP levels, statins may not reduce…”

“…However, compared to hsCRP, the novel inflammatory marker GlycA may offer several advantages including improved analytic precision, lower intra‐individual variability, and composite (integrative) nature . Higher GlycA levels have already been shown to be independently associated with all‐cause mortality, CVD events, cancer, and other serious inflammatory‐based outcomes even after adjustment for other widely studied markers of inflammation . However, it is unclear whether GlycA is potentially modifiable.…”

Inflammatory glycoproteins in cardiometabolic disorders, autoimmune diseases and cancer

“…Fucosylated haptoglobin combined with CEA may be useful as a prognostic biomarker in colorectal cancer [106] and fucosylated haptoglobin alone may be useful for prostate cancer as it correlated with Gleason scores and biochemical recurrence after radical prostatectomy [107]. In addition, GlycA, the marker of circulating GlcNAc residues, was found to be associated with incident colorectal cancer and colorectal cancer mortality but was not associated with breast cancer or mortality from any other cancer in the WHS [108].…”

Elevated alpha-1 antitrypsin is a major component of GlycA-associated risk for future morbidity and mortality

“…Of recent interest is the GlycA biomarker, a serum NMR signal that has been shown to be highly predictive of morbidity and mortality from diverse diseases 3,4 , including cardiovascular diseases [5][6][7][8] , certain cancers [7][8][9] , type II diabetes 5,10,11 , liver diseases 5,12 , chronic inflammatory conditions 5,8 , renal failure 5 , severe infections 13 , and all-cause mortality 7,8 . Elevated GlycA levels are associated with inflammation arising from recent infection, injury, or chronic disease [14][15][16][17][18] , as well as low-grade chronic inflammation that may persist for up to a decade in otherwise apparently healthy adults 13 .…”