Abstract B79: Novel protein glycan biomarker and future colorectal cancer
Authors: Chandler Paulette D. , Akinkuolie Akintunde , Tobias Deirdre , Wang Lu , Moorthy M.V. , Ridker Paul M. , Lee I-Min , Manson JoAnn E. , Buring Julie E. , Otvos James , Mora Samia 
Published: May 2016

Background: Glycoproteins mediate inflammation and are essential for various biological functions including cell growth and division of normal and malignant tissues. We hypothesized that GlycA, a novel systemic inflammatory biomarker of protein glycan N-acetyl groups, is related to incident colorectal cancer and mortality.

Methods: Using observational follow-up of a randomized trial, we evaluated the prospective association of baseline plasma GlycA with incident colorectal cancer (CRC) risk in 27,495 female health professionals aged 45 years or older and free of cancer and cardiovascular disease in the Women's Health Study (WHS, ClinicalTrials.gov: NCT00000479) with baseline blood samples and median follow-up of 19 years.

Baseline plasma GlycA was measured by nuclear magnetic resonance spectroscopy (LipoScience, Inc, Raleigh, NC) from the N-acetyl methyl groups of N-acetylglucosamine residues located on specific glycan branches of plasma proteins (mainly from the acute phase glycoproteins 1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin and transferrin). Plasma GlycA was categorized into quartiles and per 1-standard deviation (SD) increment. All cancer and mortality endpoints were confirmed from medical records. We compared GlycA to other established biomarkers of systemic inflammation, high-sensitivity C-reactive protein (hsCRP), fibrinogen, and soluble intercellular adhesion molecule-1 (sICAM).

Results: During median follow-up of 19 years, 336 incident colorectal cancer cases and 103 colorectal cancer deaths were confirmed. In multivariable Cox regression models, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC across quartiles 1-4 of GlycA were: 1.00, 1.05 [0.74-1.51], 1.24 [0.89-1.77], 1.55 [1.09-2.20], ptrend = 0.006; and for CRC mortality they were: 1.00, 0.92 [0.47-2.80], 1.26 [0.67-2.37],and 1.46 [0.77-2.77], ptrend = 0.14. Respective HRs and 95% CIs per 1-SD increment GlycA for colorectal cancer incidence and mortality were: 1.19 [1.06-1.35], p=0.004 and 1.24 [1.00-1.54], p=0.05. HsCRP, fibrinogen, and sICAM were not significantly associated with incident CRC, and hsCRP and sICAM were not significantly associated with CRC mortality; respective ptrend&gt;0.05 across quartiles 1-4 of GlycA for incident CRC and CRC mortality.

Conclusions: In this prospective study of initially healthy women, baseline GlycA levels were associated with incident colorectal cancer and mortality, consistent with a possible role for protein glycans in the pathogenesis of colorectal cancer.

Citation Format: Paulette D. Chandler, Akintunde Akinkuolie, Deirdre Tobias, Lu Wang, M.V. Moorthy, Paul M. Ridker, I-Min Lee, JoAnn E. Manson, Julie E. Buring, James Otvos, Samia Mora. Novel protein glycan biomarker and future colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B79.