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Plasma Folate, Vitamin B₆, Vitamin B₁₂, and Homocysteine and Pancreatic Cancer Risk in Four Large Cohorts

¹ Channing Laboratory, Department of Medicine, and ² Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School; ³ Department of Adult Oncology, Dana-Farber Cancer Institute; ⁴ Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School; Departments of ⁵ Epidemiology and ⁶ Nutrition, Harvard School of Public Health, Boston, Massachusetts; ⁷ Ludwig Boltzmann-Institute for Applied Cancer Research, KFJ-Spital; ⁸ Applied Cancer Research, Institute for Translational Research Vienna (ACR-ITR VIEnna), Vienna, Austria; ⁹ University of Washington School of Nursing, Seattle, Washington; ¹⁰ Department of Nutrition, College of Agriculture and Life Sciences and ¹¹ Arizona Cancer Center, University of Arizona, Tucson, Arizona

Requests for reprints: Eva S. Schernhammer, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. Phone: 617-525-4648; Fax: 617-525-2008; E-mail: eva.schernhammer{at}channing.harvard.edu.

Folate deficiency induces DNA breaks and may alter cellular capacity for mutation and epigenetic methylation. Few studies have examined the influence of one-carbon nutrients on pancreatic cancer risk, although recent studies suggest a potential protective effect for one-carbon nutrients from food sources, but not from supplements. We conducted a prospective nested case-control study to examine plasma concentrations of folate, vitamin B₆ [whose main circulating form is pyridoxal-5'-phosphate (PLP)], vitamin B₁₂, and homocysteine in relationship to pancreatic cancer, using four large prospective cohorts. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. All statistical tests were two sided. Among 208 cases and 623 controls, we observed no association between folate, PLP, vitamin B₁₂, or homocysteine and pancreatic cancer risk. Comparing the highest to lowest quartiles of plasma concentration, the ORs were 1.20 (95% CI, 0.76–1.91) for folate, 0.80 (95% CI, 0.51–1.25) for B₆, 0.91 (95% CI, 0.57–1.46) for B₁₂, and 1.43 (95% CI, 0.90–2.28) for homocysteine. In analyses restricted to nonusers of multivitamins, we observe a modest inverse trend between folate, PLP, and B₁₂ and pancreatic cancer risk. In contrast, no such inverse associations were observed among study subjects who reported multivitamin supplement use. Among all participants, plasma levels of folate, B₆, B₁₂, and homocysteine were not associated with a significant reduction in the risk of pancreatic cancer. Among participants who obtain these factors exclusively through dietary sources, there may be an inverse relation between circulating folate, B₆, and B₁₂ and risk. [Cancer Res 2007;67(11):5553–60]

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