Some reports have associated iron with cancer risk particularly of the colo
rectum. 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 hemochr
omatosis. Medline was searched for published reports using the key words ir
on, cancer, colon, rectum, ferritin, transferrin, and hemochromatosis. In a
ddition, the Cochrane Library was searched for relevant studies and several
authors were contacted to investigate their awareness of unpublished studi
es. Studies were categorized by study design and ranked for quality of inno
vation in design, sample size, and thoroughness of iron status ascertainmen
t. Thirty-three studies were reviewed in 26 publications. Of the larger stu
dies, approximately three-quarters supported the association of iron, in al
l three strata of exposure, with colorectal neoplasia risk. Because iron is
broadly supplemented in the American diet, the benefits of iron supplement
ation need to be measured against the long-term risks of increased iron exp
osure, one of which may be increased risk of colorectal cancer.