Reducing iron through regular phlebotomies is associated with a lower incidence of cancer, according to research published in the July 16 issue of the Journal of the National Cancer Institute.

Leo R. Zacharski, M.D., of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and colleagues analyzed data from 1,277 subjects, nearly all males and with a mean age of 67. All were free of visceral malignancy in the previous five years. Subjects were randomized to a control group or to receive phlebotomy every six months to maintain trough ferritin levels of about 25 ng/mL and peak ferritin levels before the next phlebotomy of about 60 ng/mL. Patients were followed for an average of 4.5 years.

The phlebotomy group had a lower risk of new cancer diagnosis (hazard ratio 0.65), the investigators report. In patients with new cancers, those who underwent iron reduction had lower cancer-specific and all-cause mortality (hazard ratios 0.39 and 0.49, respectively).

"Almost all the effects observed in the present study between the phlebotomy arm and control arm regarding cumulative incidence were seen within the first two years of entry to the study. The authors speculate that late-stage effects of iron depletion on already established tumors might be prominent, but we remain skeptical. The observed risk difference is unexpected in terms of both timing and magnitude," write Gustaf Edgren, Ph.D., of the Karolinska Institute in Stockholm, Sweden, and colleagues, in an accompanying editorial. "The possibility of bias must be seriously entertained."

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