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Circulating Folate and Folic Acid Concentrations: Associations With Colorectal Cancer Recurrence and Survival.
Geijsen, Anne J M R; Ulvik, Arve; Gigic, Biljana; Kok, Dieuwertje E; van Duijnhoven, Fränzel J B; Holowatyj, Andreana N; Brezina, Stefanie; van Roekel, Eline H; Baierl, Andreas; Bergmann, Michael M; Böhm, Jürgen; Bours, Martijn J L; Brenner, Hermann; Breukink, Stéphanie O; Bronner, Mary P; Chang-Claude, Jenny; de Wilt, Johannes H W; Grady, William M; Grünberger, Thomas; Gumpenberger, Tanja; Herpel, Esther; Hoffmeister, Michael; Huang, Lyen C; Jedrzkiewicz, Jolanta D; Keulen, Eric T P; Kiblawi, Rama; Kölsch, Torsten; Koole, Janna L; Kosma, Katharina; Kouwenhoven, Ewout A; Kruyt, Flip M; Kvalheim, Gry; Li, Christopher I; Lin, Tengda; Ose, Jennifer; Pickron, T Bartley; Scaife, Courtney L; Schirmacher, Peter; Schneider, Martin A; Schrotz-King, Petra; Singer, Marie C; Swanson, Eric R; van Duijvendijk, Peter; van Halteren, Henk K; van Zutphen, Moniek; Vickers, Kathy; Vogelaar, F Jeroen; Wesselink, Evertine; Habermann, Nina; Ulrich, Alexis B.
Affiliation
  • Geijsen AJMR; Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.
  • Ulvik A; BEVITAL, Bergen, Norway.
  • Gigic B; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
  • Kok DE; Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.
  • van Duijnhoven FJB; Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.
  • Holowatyj AN; Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Brezina S; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
  • van Roekel EH; Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
  • Baierl A; Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
  • Bergmann MM; Department of Statistics and Operations Research, University of Vienna, Vienna, Austria.
  • Böhm J; Department of Surgery, Medical University Vienna, Vienna, Austria.
  • Bours MJL; Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Brenner H; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
  • Breukink SO; Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
  • Bronner MP; Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
  • Chang-Claude J; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • de Wilt JHW; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Grady WM; Department of Surgery, GROW School for Oncology and Development Biology, Maastricht University, Maastricht, the Netherlands.
  • Grünberger T; Department of Pathology, University of Utah, Salt Lake City, UT, USA.
  • Gumpenberger T; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
  • Herpel E; Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Hoffmeister M; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Huang LC; Department of Surgery, Kaiser Franz Josef Hospital, Vienna, Austria.
  • Jedrzkiewicz JD; Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria.
  • Keulen ETP; Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
  • Kiblawi R; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kölsch T; Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Koole JL; Department of Pathology, University of Utah, Salt Lake City, UT, USA.
  • Kosma K; Department of Internal Medicine and Gastroenterology, Zuyderland Medical Center, Sittard, the Netherlands.
  • Kouwenhoven EA; Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Kruyt FM; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
  • Kvalheim G; Medical Faculty, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
  • Li CI; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
  • Lin T; Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
  • Ose J; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Pickron TB; Department of Surgery, Hospital Group Twente ZGT, Almelo, the Netherlands.
  • Scaife CL; Department of Surgery, Hospital Gelderse Vallei, Ede, the Netherlands.
  • Schirmacher P; BEVITAL, Bergen, Norway.
  • Schneider MA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Schrotz-King P; Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Singer MC; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
  • Swanson ER; Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • van Duijvendijk P; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
  • van Halteren HK; Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • van Zutphen M; Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • Vickers K; Department of Surgery, Kaiser Franz Josef Hospital, Vienna, Austria.
  • Vogelaar FJ; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
  • Wesselink E; Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
  • Habermann N; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Ulrich AB; Department of Surgery, University of Utah, Salt Lake City, UT, USA.
JNCI Cancer Spectr ; 4(5): pkaa051, 2020 Oct.
Article in En | MEDLINE | ID: mdl-33134831
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Observational_studies / Risk_factors_studies Language: En Journal: JNCI Cancer Spectr Year: 2020 Document type: Article Affiliation country: Netherlands
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Observational_studies / Risk_factors_studies Language: En Journal: JNCI Cancer Spectr Year: 2020 Document type: Article Affiliation country: Netherlands