Prediagnostic plasma folate and the risk of death in patients with colorectal cancer

Purpose Although previous studies have demonstrated an inverse relationship between folate intake and colorectal cancer risk, a recent trial suggests that supplemental folic acid may accelerate tumorigenesis among patients with a history of colorectal adenoma. Therefore, high priority has been given to research investigating the influence of folate on cancer progression in patients with colorectal cancer. Patients and Methods To investigate whether prediagnostic levels of plasma folate are associated with colorectal cancer-specific and overall mortality, we performed a prospective, nested observational study within two large US cohorts: the Nurses' Health Study and Health Professionals Follow-Up Study. We measured folate levels among 301 participants who developed colorectal cancer 2 or more years after their plasma was collected and compared participants using Cox proportional hazards models by quintile of plasma folate. Results Higher levels of plasma folate were not associated with an increased risk of colorectal cancer specific or overall mortality. Compared with participants in the lowest quintile of plasma folate, those in the highest quintile experienced a multivariable-adjusted hazard ratio for colorectal cancer-specific mortality of 0.42 (95% CI, 0.20 0.88) and overall mortality of 0.46 ( 95% CI, 0.24 0.88). When the analysis was limited to participants whose plasma was collected within 5 years of cancer diagnosis, no detrimental effect of high plasma folate was noted. In subgroup analyses, no subgroup demonstrated worse survival among participants with higher plasma folate levels. Conclusion In two large prospective cohorts, higher prediagnostic levels of plasma folate were not associated with an increased risk of colorectal cancer-specific or overall mortality.