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

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