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

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.

SUBMITTER: Geijsen AJMR

PROVIDER: S-EPMC7583160 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Geijsen Anne J M R AJMR Ulvik Arve A Gigic Biljana B Kok Dieuwertje E DE van Duijnhoven Fränzel J B FJB Holowatyj Andreana N AN Brezina Stefanie S van Roekel Eline H EH Baierl Andreas A Bergmann Michael M MM Böhm Jürgen J Bours Martijn J L MJL Brenner Hermann H Breukink Stéphanie O SO Bronner Mary P MP Chang-Claude Jenny J de Wilt Johannes H W JHW Grady William M WM Grünberger Thomas T Gumpenberger Tanja T Herpel Esther E Hoffmeister Michael M Huang Lyen C LC Jedrzkiewicz Jolanta D JD Keulen Eric T P ETP Kiblawi Rama R Kölsch Torsten T Koole Janna L JL Kosma Katharina K Kouwenhoven Ewout A EA Kruyt Flip M FM Kvalheim Gry G Li Christopher I CI Lin Tengda T Ose Jennifer J Pickron T Bartley TB Scaife Courtney L CL Schirmacher Peter P Schneider Martin A MA Schrotz-King Petra P Singer Marie C MC Swanson Eric R ER van Duijvendijk Peter P van Halteren Henk K HK van Zutphen Moniek M Vickers Kathy K Vogelaar F Jeroen FJ Wesselink Evertine E Habermann Nina N Ulrich Alexis B AB Ueland Per M PM Weijenberg Matty P MP Gsur Andrea A Ulrich Cornelia M CM Kampman Ellen E

JNCI cancer spectrum 20200707 5

<h4>Background</h4>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.<h4>Methods</h4>Circulating concentrations of folate, folic acid, and fol ...[more]

PMID: 33134831

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Project description:PurposeThe 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.ParticipantsThe 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 dateAn 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 plansBetter 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.

Dataset Information

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

Publications

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

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