TY - JOUR
T1 - One-carbon metabolites, B vitamins and associations with systemic inflammation and angiogenesis biomarkers among colorectal cancer patients
T2 - results from the ColoCare Study
AU - Kiblawi, Rama
AU - Holowatyj, Andreana N.
AU - Gigic, Biljana
AU - Brezina, Stefanie
AU - Geijsen, Anne J. M. R.
AU - Ose, Jennifer
AU - Lin, Tengda
AU - Hardikar, Sheetal
AU - Himbert, Caroline
AU - Warby, Christy A.
AU - Boehm, Juergen
AU - Bourse, Martijn J. L.
AU - van Duijnhoven, Fraenzel J. B.
AU - Gumpenberger, Tanja
AU - Kok, Dieuwertje E.
AU - Koole, Janna L.
AU - van Roekel, Eline H.
AU - Schrotz-King, Petra
AU - Ulvikl, Arve
AU - Gsur, Andrea
AU - Habermann, Nina
AU - Weijenberg, Matty P.
AU - Ueland, Per Magne
AU - Schneiders, Martin
AU - Ulrich, Alexis
AU - Ulrich, Cornelia M.
AU - Playdon, Mary
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health/National Cancer Institute (U01 CA206110, R01 CA189184 and R01 CA207371 to C. M. U.), the German Consortium of Translational Cancer Research (DKTK) and the German Cancer Research Center, the Matthias Lackas Foundation, Stiftung LebensBlicke, and Claussen-Simon Stiftung (Germany), and the Huntsman Cancer Foundation. This work was also supported by the ERA-NET, JTC 2012 call on Translational Cancer Research (TRANSCAN), JTC2013-FOCUS, project FOCUS I2104-B26 and the Federal Ministry of Education and Research, Germany (01KT1503). A. N. H. was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32 HG008962 from the National Human Genome Research Institute. E. H. R. was financially supported by Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant program (grant number 2016/1620). J. L. K. was supported by a grant from Kankeronderzoekfonds Limburg as part of Health Foundation Limburg (Grant No. 00005739). The research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA042014. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. None of the funding institutions had any role in the design, analysis or writing of this article.
Publisher Copyright:
© The Authors 2020.
PY - 2020/5/28
Y1 - 2020/5/28
N2 - B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
AB - B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
KW - One-carbon metabolism
KW - B vitamins
KW - Folate
KW - Vitamin B-6
KW - Inflammation
KW - Colorectal cancer
KW - Angiogenesis
KW - C-REACTIVE PROTEIN
KW - FOLIC-ACID SUPPLEMENTATION
KW - PYRIDOXAL 5'-PHOSPHATE
KW - PLASMA HOMOCYSTEINE
KW - THIAMINE-DEFICIENCY
KW - OXIDATIVE STRESS
KW - RISK
KW - FOLATE
KW - CATABOLISM
KW - ASPIRIN
U2 - 10.1017/S0007114520000422
DO - 10.1017/S0007114520000422
M3 - Article
C2 - 32019627
SN - 0007-1145
VL - 123
SP - 1187
EP - 1200
JO - British Journal of Nutrition
JF - British Journal of Nutrition
IS - 10
M1 - PII S0007114520000422
ER -