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

Paulette D Chandler, Akintunde O Akinkuolie, Deirdre K Tobias, Patrick R Lawler, Chungying Li, M Vinayaga Moorthy, Lu Wang, Daniel A Duprez, David R Jacobs, Robert J Glynn, James Otvos, Margery A Connelly, Wendy S Post, Paul M Ridker, JoAnn E Manson, Julie E Buring, I-Min Lee, Samia Mora, Paulette D Chandler, Akintunde O Akinkuolie, Deirdre K Tobias, Patrick R Lawler, Chungying Li, M Vinayaga Moorthy, Lu Wang, Daniel A Duprez, David R Jacobs, Robert J Glynn, James Otvos, Margery A Connelly, Wendy S Post, Paul M Ridker, JoAnn E Manson, Julie E Buring, I-Min Lee, Samia Mora

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.

Conflict of interest statement

We have the following interests: Samia Mora 500 has received research support from NHLBI, AstraZeneca, and Atherotech Diagnostics; and served as a consultant to Lilly, Pfizer, and Cerenis Therapeutics. Paul Ridker has received research support from AstraZeneca, Novartis, Roche, and Sanofi-Aventis; Paul Ridker and Brigham and Women’s Hospital have patents for the use of inflammatory biomarkers for cardiovascular disease and diabetes. Margery A. Connolly and James D. Otvos are employees of LabCorp. Provisional Patent Application (Paulette Chandler, Samia Mora, and James Otvos) filed June 3, 2016, entitled “Methods and Systems for Predicting Colorectal Cancer Incidence and Mortality" (patent application serial number 62/345,453). There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Colorectal Cancer Cumulative Incidence According…
Fig 1. Colorectal Cancer Cumulative Incidence According to GlycA Quartile in WHS (a); Colorectal Cancer Cumulative Incidence According to MESA GlycA Tertiles (b).
Fig 2. Hazard Ratios and 95% confidence…
Fig 2. Hazard Ratios and 95% confidence intervals per GlycA SD for Incident Colorectcal Cancer in Subgroups (a); Hazard Ratios and 95% confidence intervals per GlycA SD for Incident Colorectal Cancer Tumor Characteristics (Stage, Location, Grade) (b).
Fig 3. Pooled Associations between GlycA and…
Fig 3. Pooled Associations between GlycA and Colorectal Cancer Incidence and Mortality.

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