Translational research on tertiary prevention in cancer patients

Colorectal cancer (CRC) is the second leading cause of cancer death. At the same time, the number of survivors of CRC in the population continues to increase. Many cancer patients resort to taking nutritional supplements, assuming potentially beneficial effects. 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 patient cohorts this study will investigate, comprehensively, the role of folate from diet and supplements, the impact on one-carbon related biomarkers, and their joint influence on clinical outcomes, including recurrence, survival and treatment toxicity. Our study aims to investigate whether prognosis (disease-free and overall survival) in stage I-III CRC is related to folate status at different time-intervals from diagnosis to 6 month after treatment in a multicenter European cohort of 1584 CRC patients with participation from 2 Dutch, 1 Austrian, and 1 German centre. Specifically, we aim to a) determine the association of folate intake with CRC prognosis and treatment toxicity, b) determine the association of biomarkers related to one carbon metabolism with folate intake and CRC prognosis, and c) explore whether prognosis after chemotherapy differs by specific components of folate status. We expect that by unraveling the effect of folate and related biomarkers on CRC prognosis we will be able to define future tertiary prevention strategies for CRC. A first shipment of bloodsamples from the cooperating research centers arrived at the Bevital laboratory during late 2016/early 2017. Altogether 3072 blood samples were measured with 75 biomarkers (vitamins, metabolites, and protein markers) per sample. The second shipment arrived during october 2017 - january 2018. 1848 blood samples from the four cooperating centers were measured during january - march 2018 bringing the total up to 4920. After final quality control checks the data was transferred to a secure server accessible only to members of the research consortium. A report on key quantitative characteristics of each biomarker was disclosed including an overview on differences accross study centers and batch.

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.