Iron Levels in Breast Carcinogenesis

Cancer Causes Control. 2007 Sep 6; [Epub ahead of print]
Does excess iron play a role in breast carcinogenesis? an unresolved
hypothesis.Kabat GC, Rohan TE.
Department of Epidemiology and Population Health, Albert Einstein
College of Medicine, 1300 Morris Park Avenue, Room 1301, NY, 10461,
USA, gkabat@aecom.yu.edu.

Free iron is a pro-oxidant and can induce oxidative stress and DNA
damage. The carcinogenicity of iron has been demonstrated in animal
models, and epidemiologic studies have shown associations with several
human cancers. However, a possible role of excess body iron stores or
of elevated iron intake in breast carcinogenesis has received little
attention epidemiologically. We propose that iron overload and the
disruption of iron homeostasis with a resulting increase in free iron
may contribute to the development of breast cancer, and we summarize
the relevant evidence from mechanistic studies, animal experiments,
and studies in humans. Over time a high intake of iron can lead to
iron overload. Furthermore, body iron stores increase in women
following menopause. Reactive oxygen species produced by normal
aerobic cellular metabolism can lead to the release of free iron from
ferritin. In the presence of superoxide radical and hydrogen peroxide,
stored ferric iron (Fe(3+)) is reduced to ferrous iron (Fe(2+)), which
catalyzes the formation of the hydroxyl radical (*OH). *OH in turn can
promote lipid peroxidation, mutagenesis, DNA strand breaks, oncogene
activation, and tumor suppressor inhibition, increasing the risk of
breast cancer. In addition to its independent role as a proxidant,
high levels of free iron may potentiate the effects of estradiol,
ethanol, and ionizing radiation-three established risk factors for
breast cancer. In order to identify the role of iron in breast
carcinogenesis, improved biomarkers of body iron stores are needed, as
are cohort studies which assess heme iron intake. Ultimately, it is
important to determine whether iron levels in the breast and iron-
induced pathology are higher in women who go on to develop breast
cancer compared to women who do not.

PMID: 17823849 [PubMed - as supplied by publisher]


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