Abstract 34: Relationships between biomarkers of diet, one-carbon metabolism, and inflammation within the Women's Health Initiative observational study.
Authors: Paskow Michael J. , Abbenhardt Clare , Miller Joshua W. , Song Xiaoling , Brown Elissa C. , Cheng Ting-Yuan David , Wener Mark H. , Zheng Yingye , Toriola Adetunji T. , Neuhouser Marian L. , Beresford Shirley A. A. , Makar Karen , Bailey Lynn B. , Maneval David R. , Green Ralph , Manson JoAnn , Van Horn Linda , Ulrich Cornelia 
Published: August 2013

Background: Folate-mediated one-carbon metabolism is essential for DNA synthesis, repair, and methylation. Perturbations in associated biomarkers have been implicated in increased risk of colorectal cancer. Inflammation, especially related to inflammatory bowel disease, is also implicated as a risk factor for colorectal cancer, and one-carbon nutrients, particularly vitamins B6 and B12, may directly affect inflammatory processes. A concurrent investigation of these two interrelated pathways could yield new information regarding relationships between inflammatory processes and one-carbon metabolism.

Objective: To investigate correlations between nutritional, inflammatory, and one-carbon metabolism biomarkers.

Methods: A cross-sectional study design was used to explore correlations between biomarkers of nutrition, inflammation and one-carbon metabolism in 1,976 women selected from the 93,676 participants in the Women's Health Initiative Observational Study. Nutritional biomarkers included vitamin B6 (pyridoxal-5'-phosphate [PLP]), vitamin B12, plasma folate, and red blood cell (RBC) folate. C-reactive protein (CRP) and serum amyloid A (SAA) were used as biomarkers of inflammation. Homocysteine and cysteine levels were measured as integrated biomarkers of one-carbon metabolism. All biomarkers were measured using established methods from samples obtained at baseline. SAS 9.2 was used to perform Student's t, Chi-squared, and Spearman rank correlation tests, along with multivariate linear regressions adjusted for age and body mass index (BMI), to explore the relationships between the biomarkers, with statistical significance at p&lt;0.05.

Results: Plasma PLP was the only nutritional one-carbon metabolism biomarker to show significant inverse correlations with both CRP and SAA (r=-0.22, -0.12 respectively; p&lt;0.0001). A similar result was also observed when PLP [nmol/L] was regressed on CRP [mg/L] and SAA [mg/L] (adjusted regression coefficient [β]=-1.41, -0.89 respectively; p&lt;0.0001). While cysteine [μmol/L] was significantly correlated with PLP and plasma folate, and showed a significant association with CRP (β=-2.19, p&lt;0.0001), homocysteine [μmol/L] showed significant inverse correlations with all nutritional biomarkers, and was significantly associated with both CRP (β=19.86, p=0.003) and SAA (β=25.62, p&lt;0.0001).

Conclusions: Biomarkers of inflammation are associated with concentrations of PLP, cysteine and homocysteine. While these associations between the biomarkers of inflammation, diet, and one-carbon metabolism are promising, determining causality is an important next step.

Citation Format: Michael J. Paskow, Clare Abbenhardt, Joshua W. Miller, Xiaoling Song, Elissa C. Brown, Ting-Yuan David Cheng, Mark H. Wener, Yingye Zheng, Adetunji T. Toriola, Marian L. Neuhouser, Shirley A. A. Beresford, Karen Makar, Lynn B. Bailey, David R. Maneval, Ralph Green, JoAnn Manson, Linda Van Horn, Cornelia Ulrich. Relationships between biomarkers of diet, one-carbon metabolism, and inflammation within the Women's Health Initiative observational study. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 34.