Plasma folate, vitamin B₆, Vitamin B₁₂, and homocysteine and pancreatic cancer risk in four large cohorts

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.