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Some reports have associated iron with cancer risk, particularly of the colorectum. This review will focus on the human studies that have investigated this association. Comparative studies were sought in which people with and without colorectal neoplastic lesions, either cancers or adenomatous polyps, were assessed for iron exposure. Iron exposure variables included dietary iron intake, iron vitamin supplementation, body iron stores as measured by ferritin or transferrin saturation, and gene status for hereditary hemochromatosis. Medline was searched for published reports using the key words iron, cancer, colon, rectum, ferritin, transferrin, and hemochromatosis. In addition, the Cochrane Library was searched for relevant studies and several authors were contacted to investigate their awareness of unpublished studies. Studies were categorized by study design and ranked for quality of innovation in design, sample size, and thoroughness of iron status ascertainment. Thirty-three studies were reviewed in 26 publications. Of the larger studies, approximately three-quarters supported the association of iron, in all three strata of exposure, with colorectal neoplasia risk. Because iron is broadly supplemented in the American diet, the benefits of iron supplementation need to be measured against the long-term risks of increased iron exposure, one of which may be increased risk of colorectal cancer.