Circulating Folate and Folic Acid Concentrations: Associations With Colorectal Cancer Recurrence and Survival-Reference-Cited by-同舟云学术

Circulating Folate and Folic Acid Concentrations: Associations With Colorectal Cancer Recurrence and Survival

Published:2020-07-07 Issue:5 Volume:4 Page:
ISSN:2515-5091
Container-title:JNCI Cancer Spectrum
language:en
Short-container-title:

Author:

Geijsen Anne J M R¹^ORCID,Ulvik Arve²,Gigic Biljana³^ORCID,Kok Dieuwertje E¹^ORCID,van Duijnhoven Fränzel J B¹^ORCID,Holowatyj Andreana N⁴⁵^ORCID,Brezina Stefanie⁶,van Roekel Eline H⁷,Baierl Andreas⁸^ORCID,Bergmann Michael M⁹^ORCID,Böhm Jürgen⁴⁵,Bours Martijn J L⁷,Brenner Hermann¹⁰¹¹¹²,Breukink Stéphanie O¹³,Bronner Mary P¹⁴,Chang-Claude Jenny¹⁵^ORCID,de Wilt Johannes H W¹⁶,Grady William M¹⁷^ORCID,Grünberger Thomas¹⁸,Gumpenberger Tanja⁶^ORCID,Herpel Esther¹⁹,Hoffmeister Michael¹¹,Huang Lyen C⁴^ORCID,Jedrzkiewicz Jolanta D¹⁴^ORCID,Keulen Eric T P²⁰,Kiblawi Rama⁴⁵²¹^ORCID,Kölsch Torsten³,Koole Janna L⁷^ORCID,Kosma Katharina¹⁷,Kouwenhoven Ewout A²²,Kruyt Flip M²³,Kvalheim Gry²,Li Christopher I²⁴,Lin Tengda⁴⁵,Ose Jennifer⁴⁵^ORCID,Pickron T Bartley⁴,Scaife Courtney L⁴,Schirmacher Peter¹⁸,Schneider Martin A³,Schrotz-King Petra¹⁰^ORCID,Singer Marie C¹⁷,Swanson Eric R²⁵,van Duijvendijk Peter²⁶^ORCID,van Halteren Henk K²⁷,van Zutphen Moniek¹^ORCID,Vickers Kathy²³,Vogelaar F Jeroen²⁸,Wesselink Evertine¹^ORCID,Habermann Nina²⁹,Ulrich Alexis B³,Ueland Per M²,Weijenberg Matty P⁷,Gsur Andrea⁶^ORCID,Ulrich Cornelia M⁴⁵,Kampman Ellen¹

Affiliation:

1. Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands

2. BEVITAL, Bergen, Norway

3. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

4. Huntsman Cancer Institute, Salt Lake City, UT, USA

5. Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA

6. Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Vienna, Austria

7. Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands

8. Department of Statistics and Operations Research, University of Vienna, Vienna, Austria

9. Department of Surgery, Medical University Vienna, Vienna, Austria

10. Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany

11. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

12. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

13. Department of Surgery, GROW School for Oncology and Development Biology, Maastricht University, Maastricht, the Netherlands

14. Department of Pathology, University of Utah, Salt Lake City, UT, USA

15. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany

16. Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Radboud University Medical Center, Nijmegen, the Netherlands

17. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

18. Department of Surgery, Kaiser Franz Josef Hospital, Vienna, Austria

19. Institute of Pathology, University of Heidelberg, Heidelberg, Germany

20. Department of Internal Medicine and Gastroenterology, Zuyderland Medical Center, Sittard, the Netherlands

21. Medical Faculty, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany

22. Department of Surgery, Hospital Group Twente ZGT, Almelo, the Netherlands

23. Department of Surgery, Hospital Gelderse Vallei, Ede, the Netherlands

24. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

25. Department of Surgery, University of Utah, Salt Lake City, UT, USA

26. Department of Surgery, Gelre Hospital, Apeldoorn, the Netherlands

27. Department of Internal Medicine, Admiraal de Ruyter Hospital, Goes, the Netherlands

28. Department of Surgery, VieCuri Medical Center, Venlo, the Netherlands

29. Genome Biology, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany

Abstract

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.

Funder

Wereld Kanker Onderzoek Fonds

World Cancer Research Fund International

World Cancer Research Fund International Regular Grant Programme

Alpe d’Huzes/Dutch Cancer Society

ERA-NET on Translational Cancer Research

Netherlands Organization for Health Research and Development

Austrian Science Fund

Federal Ministry of Education and Research

Research Council of Norway

National Cancer Institute

Huntsman Cancer Foundation