1. Circulating Folate and Folic Acid Concentrations: Associations With Colorectal Cancer Recurrence and Survival
- Author
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Matty P. Weijenberg, Per Magne Ueland, Jolanta Jedrzkiewicz, Stephanie O. Breukink, Jennifer Ose, Petra Schrotz-King, Jenny Chang-Claude, F. Jeroen Vogelaar, Anne J.M.R. Geijsen, Torsten Kölsch, Alexis Ulrich, Peter Schirmacher, Fränzel J.B. van Duijnhoven, Janna L. Koole, Tengda Lin, Biljana Gigic, Johannes H. W. de Wilt, Courtney L. Scaife, Eric T.P. Keulen, Flip M. Kruyt, Eline H. van Roekel, William M. Grady, Dieuwertje E. Kok, Ellen Kampman, Martijn J.L. Bours, Henk K. van Halteren, Tanja Gumpenberger, Martin Schneider, Michael Hoffmeister, Cornelia M. Ulrich, Mary P. Bronner, Andreas Baierl, Katharina Kosma, Nina Habermann, Rama Kiblawi, Eric R. Swanson, Gry Kvalheim, Moniek van Zutphen, Andrea Gsur, Marie C Singer, Arve Ulvik, Evertine Wesselink, Hermann Brenner, Ewout A. Kouwenhoven, T Bartley Pickron, Peter van Duijvendijk, Jürgen Böhm, Andreana N. Holowatyj, Kathy Vickers, Stefanie Brezina, Esther Herpel, Christopher I. Li, Thomas Grünberger, Lyen C. Huang, Michael Bergmann, Epidemiologie, RS: GROW - R1 - Prevention, Surgery, MUMC+: MA Heelkunde (9), and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
- Subjects
Cancer Research ,medicine.medical_specialty ,Nutrition and Disease ,Colorectal cancer ,BIOMARKERS ,VITAMINS ,METABOLISM ,medicine.disease_cause ,Gastroenterology ,Article ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,03 medical and health sciences ,0302 clinical medicine ,Dual role ,Voeding en Ziekte ,Internal medicine ,medicine ,Life Science ,TANDEM MASS-SPECTROMETRY ,Stage (cooking) ,VLAG ,030304 developmental biology ,0303 health sciences ,PLASMA ,business.industry ,Hazard ratio ,medicine.disease ,Confidence interval ,Oncology ,Folic acid ,030220 oncology & carcinogenesis ,CATABOLITES ,NUTRITION ,DIHYDROFOLATE-REDUCTASE ,AcademicSubjects/MED00010 ,HUMAN SERUM ,Carcinogenesis ,business ,Cohort study - Abstract
Background Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown. Methods Circulating concentrations of folate, folic acid, and folate catabolites p-aminobenzoylglutamate and p-acetamidobenzoylglutamate were measured by liquid chromatography-tandem mass spectrometry at diagnosis in 2024 stage I-III colorectal cancer patients from European and US patient cohort studies. Multivariable-adjusted Cox proportional hazard models were used to assess associations between folate, folic acid, and folate catabolites concentrations with recurrence, overall survival, and disease-free survival. Results No statistically significant associations were observed between folate, p-aminobenzoylglutamate, and p-acetamidobenzoylglutamate concentrations and recurrence, overall survival, and disease-free survival, with hazard ratios ranging from 0.92 to 1.16. The detection of folic acid in the circulation (yes or no) was not associated with any outcome. However, among patients with detectable folic acid concentrations (n = 296), a higher risk of recurrence was observed for each twofold increase in folic acid (hazard ratio = 1.31, 95% confidence interval = 1.02 to 1.58). No statistically significant associations were found between folic acid concentrations and overall and disease-free survival. Conclusions Circulating folate and folate catabolite concentrations at colorectal cancer diagnosis were not associated with recurrence and survival. However, caution is warranted for high blood concentrations of folic acid because they may increase the risk of colorectal cancer recurrence.
- Published
- 2020
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