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.
Bibliographical noteFunding Information:
The WHS 529 is supported by grants CA-047988, HL-043851, HL-530 080467, HL-099355, and UM1 CA182913 from the National Institutes of Health, Bethesda, MD. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC- 95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-534 HC-95163, N01-HC-95164, N01-HC-95165, N01-HC- 95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and CTSA UL1-RR-024156. P.D. Chandler received support from grant 127524-MRSG-15-012-01-CNE from the American Cancer Society. A.O. Akinkoulie and P.R. Lawler received support from NIH T32 (HL007575). D.K. Tobias is supported by a Mentored Research Scientist Development Award from the NIH NIDDK (K01DK103720). The biomarker measurements were supported by the Donald W. Reynolds Foundation, the Foundation Leducq, and the American Heart Association. Margery A. Connolly and James D. Otvos are employees of LabCorp. LabCorp provided support in the form of salaries for authors MAC and JDO, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. LipoScience (now LabCorp; Raleigh, NC) performed the analysis of GlycA based on LipoProfile-3 at no additional cost to the studies but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. These funding agencies had no role in the design and execution of the current study. The specific roles of these authors are articulated in the "author contributions" section.
© 2016 Chandler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.