Association of N-Linked Glycoprotein Acetyls and Colorectal Cancer Incidence and Mortality
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Akinkuolie, Akintunde O.
Li, Chungying
Moorthy, M. Vinayaga
Duprez, Daniel A.
Jacobs, David R.
Otvos, James
Connelly, Margery A.
Post, Wendy S.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pone.0165615Metadata
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Chandler, P. D., A. O. Akinkuolie, D. K. Tobias, P. R. Lawler, C. Li, M. V. Moorthy, L. Wang, et al. 2016. “Association of N-Linked Glycoprotein Acetyls and Colorectal Cancer Incidence and Mortality.” PLoS ONE 11 (11): e0165615. doi:10.1371/journal.pone.0165615. http://dx.doi.org/10.1371/journal.pone.0165615.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 NCT00005487Other Sources
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