Does excess iron play a role in breast carcinogenesis? An unresolved hypothesis

Geoffrey C. Kabat, Thomas E. Rohan

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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 (Fe2+), 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.

Original languageEnglish (US)
Pages (from-to)1047-1053
Number of pages7
JournalCancer Causes and Control
Volume18
Issue number10
DOIs
StatePublished - Dec 2007

Fingerprint

Carcinogenesis
Breast
Iron
Breast Neoplasms
Iron Overload
Reactive Oxygen Species
DNA Breaks
Ferritins
Menopause
Ionizing Radiation
Heme
Oncogenes
Mutagenesis
Superoxides
Hydroxyl Radical
Hydrogen Peroxide
Lipid Peroxidation
DNA Damage
Epidemiologic Studies
Estradiol

Keywords

  • Breast neoplasms
  • Heme iron
  • Iron
  • Lipid peroxidation
  • Reactive oxygen species

ASJC Scopus subject areas

  • Oncology
  • Epidemiology
  • Cancer Research

Cite this

Does excess iron play a role in breast carcinogenesis? An unresolved hypothesis. / Kabat, Geoffrey C.; Rohan, Thomas E.

In: Cancer Causes and Control, Vol. 18, No. 10, 12.2007, p. 1047-1053.

Research output: Contribution to journalArticle

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