Cohort profile: Biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer recurrence and survival - the FOCUS Consortium

Biljana Gigic, Eline van Roekel, Andreana N Holowatyj, Stefanie Brezina, Anne J M R Geijsen, Arve Ulvik, Jennifer Ose, Janna L Koole, Victoria Damerell, Rama Kiblawi, Tanja Gumpenberger, Tengda Lin, Gry Kvalheim, Torsten Koelsch, Dieuwertje E Kok, Franzel J van Duijnhoven, Martijn J Bours, Andreas Baierl, Christopher I Li, William GradyKathy Vickers, Nina Habermann, Martin Schneider, Ellen Kampman, Per Magne Ueland, Alexis Ulrich, Matty Weijenberg, Andrea Gsur, Cornelia Ulrich*, FOCUS Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


PURPOSE: The overarching goal of the FOCUS (biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer (CRC) recurrence and survival) Consortium is to unravel the effect of folate and folate-mediated one-carbon metabolism (FOCM) biomarkers on CRC prognosis to provide clinically relevant advice on folate intake to cancer patients and define future tertiary prevention strategies.

PARTICIPANTS: The FOCUS Consortium is an international, prospective cohort of 2401 women and men above 18 years of age who were diagnosed with a primary invasive non-metastatic (stages I-III) CRC. The consortium comprises patients from Austria, two sites from the Netherlands, Germany and two sites from the USA. Patients are recruited after CRC diagnosis and followed at 6 and 12 months after enrolment. At each time point, sociodemographic data, data on health behaviour and clinical data are collected, blood samples are drawn.

FINDINGS TO DATE: An increased risk of cancer recurrences was observed among patients with higher compared with lower circulating folic acid concentrations. Furthermore, specific folate species within the FOCM pathway were associated with both inflammation and angiogenesis pathways among patients with CRC. In addition, higher vitamin B6 status was associated with better quality of life at 6 months post-treatment.

FUTURE PLANS: Better insights into the research on associations between folate and FOCM biomarkers and clinical outcomes in patients with CRC will facilitate the development of guidelines regarding folate intake in order to provide clinically relevant advice to patients with cancer, health professionals involved in patient care, and ultimately further tertiary prevention strategies in the future. The FOCUS Consortium offers an excellent infrastructure for short-term and long-term research projects and for combining additional biomarkers and data resulting from the individual cohorts within the next years, for example, microbiome data, omics and multiomics data or CT-quantified body composition data.

Original languageEnglish
Article numbere062930
Number of pages17
JournalBMJ Open
Issue number12
Publication statusPublished - 22 Dec 2022


  • Male
  • Humans
  • Female
  • Folic Acid
  • Prospective Studies
  • Quality of Life
  • Biomarkers
  • Colorectal Neoplasms/metabolism
  • Carbon/metabolism

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