Reductions in Iron Blood Levels Associated with Decreased Cancer Risk in Men with Peripheral Arterial Disease

Observational studies have suggested that lower levels of iron in the blood may be associated with a reduced risk of cancer. Data from animal studies are consistent with the observation, and researchers hypothesize that iron catalyzes the production of free radicals that damage cellular components, including DNA.

The current randomized controlled trial enrolled individuals with peripheral arterial disease from Veterans Administration facilities. The primary goal of the trial was to examine the effect of reducing of iron stores on the development of vascular disease. In the current analysis, Leo Zacharski, M.D., of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and colleagues compared the rate of new visceral malignancies and cause-specific mortality in the trial participants, 98.8 percent of whom were men. The malignancy and mortality data were collected prospectively.

The 636 participants who underwent phlebotomy were 37 percent less likely to develop cancer during the 4.5-year follow-up period than were the 641 participants assigned to the control arm (38 versus 60 cancers). Individuals in the experimental arm also had a lower cancer-specific and all cause-mortality compared with individuals in the control arm.

"Findings from this study support the hypothesis that ambient levels of body iron stores represented by the serum ferritin level are associated with cancer risk and that lowering iron levels reduces cancer risk," the authors write.

In an accompanying editorial, Gustaf Edgren, Ph.D., Olof Nyrén, M.D., Ph.D., and Mads Melbye, M.D., Ph.D., of the Karolinska Institute in Stockholm and Statens Serum Institut in Copenhagen commend the study authors for their innovative and well-executed trial. The editorialists caution, however, that the trial was not designed to investigate cancer incidence and the current report is based on an ad hoc analysis. "The results are so unexpected that all possibilities for bias must be carefully examined," the editorialists write, particularly because of the timing and magnitude of the effect. "For the present, the results have to be interpreted with caution."