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Biomarkers and Early Detection: Risk Markers and Surrogate Endpoints

Plasma folate, vitamins B₆, B₁₂, and homocysteine and pancreatic cancer risk in four large cohorts.

Harvard Medical School, Boston, MA; Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, Boston, MA; University of Washington School of Nursing, Seattle, WA; Department of Nutrition, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ

Abstract

A9

Background. Folate deficiency induces DNA breaks and may elevate the risk of pancreatic cancer through altered cellularcapacity 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. Methods. 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. In this largest study to date, we combined four prospective cohort studies of women and men, participating in the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), Physicians' Health Study (PHS), and Women's Health Initiative (WHI). Multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Primary analyses excluded cases that occurred in the first two years after blood collection, leaving a total of 208 cases and 623 controls. All statistical tests were two-sided. Results. Overall, we observed no association between plasma concentrations of folate, PLP, vitamin B₁₂, or homocysteine and the subsequent risk of pancreatic cancer. Comparing the highest to lowest quartiles of plasma concentration, the ORs were 1.20 (95% Confidence Interval (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, which reached statistical significance for PLP (OR, 0.47, 95% CI, 0.24-0.92). In contrast, no such inverse associations were observed among study subjects who reported multivitamin supplement use. Conclusion. 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.