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Prediagnostic Plasma Folate and the Risk of Death in Patients With Colorectal Cancer

Brian M. Wolpin, Esther K. Wei, Kimmie Ng, Jeffrey A. Meyerhardt, Jennifer A. Chan, Jacob Selhub, Edward L. Giovannucci, Charles S. Fuchs

From the Department of Medical Oncology, Dana-Farber Cancer Institute; Channing Laboratory; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University; and the Departments of Epidemiology and Nutrition, Harvard School of Public Health, Harvard University, Boston, MA

Corresponding author: Brian Wolpin, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: bwolpin{at}partners.org

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.

Supported by Grants No. CA118553, CA87969, CA108341, and CA09001 from the National Cancer Institute, National Institutes of Health.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.