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Does excess iron play a role in breast carcinogenesis? An unresolved hypothesis.
Cancer Causes Control. 2007 Dec; 18(10):1047-53.CC

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 (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.

Authors+Show Affiliations

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY 10461, USA.. gkabat@aecom.yu.eduNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17823849

Citation

Kabat, Geoffrey C., and Thomas E. Rohan. "Does Excess Iron Play a Role in Breast Carcinogenesis? an Unresolved Hypothesis." Cancer Causes & Control : CCC, vol. 18, no. 10, 2007, pp. 1047-53.
Kabat GC, Rohan TE. Does excess iron play a role in breast carcinogenesis? An unresolved hypothesis. Cancer Causes Control. 2007;18(10):1047-53.
Kabat, G. C., & Rohan, T. E. (2007). Does excess iron play a role in breast carcinogenesis? An unresolved hypothesis. Cancer Causes & Control : CCC, 18(10), 1047-53.
Kabat GC, Rohan TE. Does Excess Iron Play a Role in Breast Carcinogenesis? an Unresolved Hypothesis. Cancer Causes Control. 2007;18(10):1047-53. PubMed PMID: 17823849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Does excess iron play a role in breast carcinogenesis? An unresolved hypothesis. AU - Kabat,Geoffrey C, AU - Rohan,Thomas E, Y1 - 2007/09/06/ PY - 2007/04/05/received PY - 2007/08/20/accepted PY - 2007/9/8/pubmed PY - 2008/4/12/medline PY - 2007/9/8/entrez SP - 1047 EP - 53 JF - Cancer causes & control : CCC JO - Cancer Causes Control VL - 18 IS - 10 N2 - 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. SN - 0957-5243 UR - https://www.unboundmedicine.com/medline/citation/17823849/Does_excess_iron_play_a_role_in_breast_carcinogenesis_An_unresolved_hypothesis_ L2 - https://doi.org/10.1007/s10552-007-9058-9 DB - PRIME DP - Unbound Medicine ER -