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.