Reducing iron stores by phlebotomy lowers cancer risk in older men

July 8, 2008

NEW YORK (Reuters Health) - Cancer incidence and mortality in older men may be reduced by repeated phlebotomy to lower serum ferritin levels, according to findings published online on July 8 in the Journal of the National Cancer Institute.

Observational studies suggest that lower body iron stores may protect against malignancy by reducing iron-induced oxidative stress, Dr. Leo R. Zacharski and his associates note.

To test this possibility, Dr. Zacharski, at the White River Junction Veterans Affairs Medical Center, Vermont, and his group conducted an ad hoc analysis of data from a VA study in which patients with peripheral arterial disease were assigned to repeated blood collections (n = 636) or to a control group (n = 641), originally for prevention of atherosclerotic complications.

The population was 99% male, mean age 67 years, with mean ferritin levels at baseline of 122 ng/mL. Phlebotomy was scheduled every 6 months to maintain ferritin levels between 25 and 60 ng/mL. During a mean follow-up of 4.5 years, there were 60 new visceral malignancies in the control patients and 38 in the iron-reduction patients (p = 0.023).

The risk of new malignancy (hazard ratio 0.65, p = 0.036) was significantly lower in the phlebotomy group. Among patients who did develop cancer, cancer-specific mortality (HR 0.39, p = 0.003) and all-cause mortality (HR 0.49, p = 0.009) were lower in the phlebotomy group.

Overall, 75% of new cancers occurred in patients with mean ferritin levels > 57 ng/mL.

These findings do not pertain to younger patients without vascular disease, women, or African Americans, whose ferritin levels are higher than those of Caucasians, the investigators say. Instead, "these observations provide incentive for future studies and insight into optimal clinical trial design."

Dr. Zacharski's team suggests "there may be a need to redefine the normal range for the serum ferritin level based on associated disease risk." They also call for re-evaluation of the policy of routinely administering iron to anemic cancer patients.

In a related editorial, Dr. Mads Melbye, at Statens Serum Institut in Copenhagen and colleagues suggest that "these results almost seem to be too good to be true."

While recommending that "all possibilities for bias must be carefully examined" and that "the results have to be interpreted with caution," the editorialists also support more research on this topic.

Furthermore, they write, "a cautious standpoint toward iron supplementation where no proper indication exists is perhaps advisable."