Role of iron in carcinogenesis: cancer as a ferrotoxic disease

Our plain-English summary of Role of iron in carcinogenesis: cancer as a ferrotoxic disease, by S. Toyokuni (Cancer Science, 2009).

The study

• Author: S. Toyokuni
• Journal: Cancer Science
• Published: 2009;100(1):9-16
• Type of article: Review
• Cited by: 385 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Iron is abundant universally. During the evolutionary processes, humans have selected iron as a carrier of oxygen inside the body. However, iron works as a double-edged sword, and its excess is a risk for cancer, presumably via generation of reactive oxygen species. Thus far, pathological conditions such as hemochromatosis, chronic viral hepatitis B and C, exposure to asbestos fibers, as well as endometriosis have been recognized as iron overload-associated risks for human cancer. Indeed, iron is carcinogenic in animal experiments. These reports unexpectedly revealed that there are target genes in iron-induced carcinogenesis and that iron-catalyzed oxidative DNA damage is not random in vivo. Several iron transporters and hepcidin, a peptide hormone regulating iron metabolism, were discovered in the past decade. Furthermore, a recent epidemiological study reported that iron reduction by phlebotomy decreased cancer risk in the apparently normal population. These results warrant reconsideration of the role of iron in carcinogenesis and suggest that fine control of body iron stores would be a wise strategy for cancer prevention.

In plain English

This article is a review, not a new study. The author described findings on iron metabolism and on how excess iron may contribute to cancer. The review listed asbestos exposure, linked to malignant mesothelioma and lung carcinoma, among four human conditions it described as associated with iron overload-associated cancer. The other three were hemochromatosis, chronic viral hepatitis B and C, and ovarian endometriosis. On asbestos, the author stated that epidemiological studies show iron-containing asbestos fibers are more carcinogenic. The author also wrote that the author's own recent study suggests local iron overload is important for asbestos-induced carcinogenesis. A table of animal models included amosite and crocidolite, described as iron-rich asbestos fibers, producing lung cancer and pleural or peritoneal mesothelioma in rats and mice. Much of the review discussed the author's laboratory's rat kidney cancer model using an iron compound, ferric nitrilotriacetate. The author concluded that iron plays an important role in oxidative tissue damage and carcinogenesis. The author also concluded that understanding iron-induced carcinogenesis should be a high priority for cancer prevention.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review
• Who was studied: No study population; the review summarized published human studies of conditions with iron overload and published animal models of iron-induced cancer, including the author's own laboratory's work
• Exposure: Iron overload and iron compounds in general. Asbestos was one of the exposures discussed, with amosite and crocidolite described as iron-rich fibers in the animal-model table.
• Main results:
  • The review's table of human conditions linked asbestos exposure to malignant mesothelioma and lung carcinoma as an iron overload-associated cancer risk.
  • Citing a published study, the author stated that epidemiological studies show iron-containing asbestos fibers are more carcinogenic.
  • The author reported that the author's own recent study suggests local iron overload is important for asbestos-induced carcinogenesis.
  • Citing animal studies, the review stated that giving asbestos fibers by inhalation, intraperitoneal or intrapleural routes causes mesothelioma and lung cancer. Its table listed amosite and crocidolite causing lung cancer and pleural or peritoneal mesothelioma in rats and mice.
  • In the review's discussion of a rat kidney cancer model induced by ferric nitrilotriacetate (from the author's laboratory), the p15 and p16 tumor-suppressor genes were reported as among the major target genes.
• The authors' conclusion: The author concluded that iron plays an important role in oxidative tissue damage and subsequent carcinogenesis. The author also concluded that full understanding of iron-induced carcinogenesis should be a high priority for cancer prevention.
• Limitations the authors state:
  • The author noted that only limited data exist on where catalytic iron is located in cells, because suitable methods are lacking.
  • The author noted that only limited data are available on which parts of the genome are susceptible to oxidative damage in living organisms.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Reactive Oxygen Species (ROS), Carcinogenic.

Related studies

• Iron addiction with ferroptosis-resistance in asbestos-induced mesothelial carcinogenesis: Toward the era of mesothelioma prevention — S. Toyokuni (2019)
• Iron as a target of chemoprevention for longevity in humans — S. Toyokuni (2011)
• The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy — S. Toyokuni (2016)
• Iron overload as a major targetable pathogenesis of asbestos-induced mesothelial carcinogenesis — S. Toyokuni (2014)
• The effect of iron binding on the ability of crocidolite asbestos to catalyze DNA single-strand breaks — J.A. Hardy, A.E. Aust (1995)
• Cancer risks among iron and steel workers in Anshan, China, Part I: Proportional mortality ratio analysis — Z. Xu, G.W. Pan, et al. (1996)

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