Title: Biomarkers related to folate-dependent one-carbon metabolism in CRC recurrence and survival.


Project Coordinator:
Andrea GSUR (Austria) Institute of Cancer Research, Medical University of Vienna, Vienna

Project Partners:
Ellen KAMPMAN (The Netherlands) Wageningen University, Wageningen
Per Magne UELAND (Norway) BEVITAL, Bergen
Matty WEIJENBERG (The Netherlands) Maastricht University, Wageningen
Alexis ULRICH (Germany), Department of General-, Visceral- and Transplant Surgery, University Clinic, Heidelberg


Project Abstract:
Colorectal cancer (CRC) is the second leading cause of cancer death. At the same time, the number of survivors of CRC continues to increase. Many cancer patients resort to taking nutritional supplements, assuming potential benefits. However, in the case of folate this assumption may be wrong, since high folate may stimulate the growth of established cancer. Folate is involved in one-carbon metabolism, impacts DNA synthesis, and supports tumor growth. Within a large consortium of parallel European CRC patient cohorts we will be able to investigate, comprehensively, the role of folate from diet and supplements, the impact on a state-of-the art set of one-carbon metabolism biomarkers, and their joint influence on clinical outcomes, including recurrence, survival and treatment toxicity. Our study aims to investigate whether prognosis in stage I-III CRC is related to folate status at different time-intervals in 1584 CRC patients. Both key biomarkers of folate-mediated one-carbon metabolism (FOCM) and diet/supplements will be investigated as components of folate status prior to surgery, and at 6 and 12 months past surgery. Further, we propose to determine whether biomarkers related to FOCM are associated with folate intake, and explore whether folate status modifies treatment toxicity in patients who underwent 5-FU chemotherapy.
We leverage unique resources and expect that by unraveling the effect of the folate and FOCM biomarkers on CRC prognosis we will be able to provide clinically relevant advice to cancer patients and define future tertiary prevention strategies.

Publishable summary:
Colorectal cancer (CRC) is the second leading cause of cancer death among both men and women. At the same time, the number of CRC survivors continues to increase. Many cancer patients resort to taking nutritional supplements, assuming potential benefits. However, in the case of folate this assumption may be wrong, since high folic acid intake may stimulate the growth of established cancerous lesions. Due to the paucity of research in this area we are far from giving evidence-based recommendations to CRC patients facing the question of using supplements containing folic acid to improve their chances of survival. The FOCUS consortium brings together large European prospective patient cohorts aiming to investigate the role of folate and folic acid from diet and supplements and the impact of one-carbon metabolism biomarkers on CRC survival. The research aim of this collaborative effort is to investigate the impact of folate-mediated one-carbon metabolism (FOCM) biomarkers in a state-of-the art set, and their joint influence on clinical outcomes, including recurrence, survival and treatment toxicity. This study leverages unique resources, targeting to unravel the effect of FOCM biomarkers on CRC prognosis. The results of this study will provide clinically relevant advice to cancer patients and define future tertiary prevention strategies.

 

(Project funded under JTC 2013)