Vitamin Link in Pancreatic Cancer Protection Still Sketchy

BOSTON, June 1 -- Folate and B vitamins from food, but not from supplements, may be of modest help in fending off cancer of the pancreas.

Combing through combined data from four large prospective cohort studies, Eva Schernhammer, M.D., Dr.P.H., of Harvard Medical School, and colleagues, found that among participants who did not take multivitamins but had high levels of folate, B₆, and B₁₂ in their diets, there was a modest decrease in risk of pancreatic cancer.

But even with such a large patient sample to work with, the evidence for a protective benefit from vitamins is far from ironclad, the authors said in the June 1 issue of Cancer Research.

"Our study does not support a clear association between circulating levels of one-carbon nutrients and the risk of pancreatic cancer," they wrote. "Among participants who achieve their intake of these factors exclusively through dietary sources, there may be an inverse relation between circulating folate, B₆, and B₁₂ and risk, particularly among subjects who maintained a normal BMI; nonetheless, such subset analyses must be viewed cautiously because of multiple comparisons and smaller sample size within exposure groups."

The investigators also found evidence to suggest that use of multivitamins could actually increase risk of pancreatic cancer. They were reluctant to make any specific clinical recommendations based on their findings.

"All we can say is that a person who has reason to be concerned about their risk of developing this cancer, which is relatively rare but quite deadly, should maintain a normal weight and eat their fruit and vegetables," said Dr. Schernhammer.

Based on recent studies suggesting a potential protective effect against pancreatic cancer from folate and other one-carbon nutrients in food, the authors looked at the relationship of dietary folate and B vitamins to cancer risk.

They conducted a nested case control study of data from four large prospective cohort studies: the Nurses' Health Study, the Health Professionals Follow-up Study, Physicians' Health Study, and Women's Health Initiative.

"Pooling of samples from these four prospective cohorts allows for a more rigorous examination of plasma micronutrients while minimizing the potential biases that are inherent in retrospective studies of pancreatic cancer epidemiology," the authors wrote.

From the 288,977 participants in the combined studies, they identified a total of 247 case patients and 740 controls, but then excluded all cases diagnosed within two years of blood drawing to avoid introducing causality bias, leaving them 208 cases, and 623 controls.

They collected data on plasma concentrations of folate, vitamin B₆ (as measured by its main circulating form pyridoxal-5'-phosphate, or PLP), vitamin B₁₂, and homocysteine in relationship to pancreatic cancer.

"Among 208 cases and 623 controls, we observed no association between folate, PLP, vitamin B₁₂, or homocysteine and pancreatic cancer risk," they wrote.

When they compared the highest to the lowest quartiles of plasma concentrations of each nutrient, they calculated the following odds ratios:

• Folate, odds ratio 1.20 (95% confidence interval, 0.76-1.91)
• B₆/PLP, odds ratio 0.80 (95% CI, 0.51-1.25)
• B₁₂, odds ratio 0.91 (95% CI, 0.57-1.46)
• Homocysteine, odds ratio 1.43 (95% CI, 0.90-2.28)

When they restricted their analyses to people who did not use multivitamins, however, they found a somewhat different story. There was a modest inverse trend between the highest and lowest quartiles for folate, PLP, and B₁₂ and pancreatic cancer risk, but this relationship reached statistical significance only for B₆/PLP (odds ratio 0.47; 95% CI, 0.24-0.92). After further adjustment for body mass index, physical activity, and a history of diabetes this relationship was somewhat weaker, however (odds ratio, 0.51, 95% CI, 0.25-1.02).

The authors also found evidence to suggest that multivitamin use or specific supplements may actually be harmful, as suggested in other recently published studies.

"Consistent with previous studies, we, too, noted a suggestion of an increased risk of pancreatic cancer risk with higher folate and PLP levels among the multivitamin users in our cohorts," the authors wrote. "The suggestion of an increased risk for pancreatic cancer among the multivitamin users requires confirmation; additional studies should further assess the influence of long-term multivitamin supplement use on pancreatic cancer risk. "

Their analysis was limited by the use of four distinct cohorts with varying means of assessing covariates, which could have had an effect on the ability to adjust for potential confounding factors. In addition, changes in dietary folate following widespread fortification of foods could also have altered the results, they acknowledged.