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The iron found in red meat plays a crucial role in colon cancer risk

At the international scale, a clear link has now been established between dietary habits and the risk of developing colon cancer. Epidemiological data suggest that 15% of colon cancer cases can be attributed to the excessive consumption of red and processed meat. To better understand and thus prevent this cancer type, INRA researchers collaborated with scientists from the National Veterinary School of Toulouse and the University of Reading in England to explore the mechanisms underlying this relationship. They discovered that the heme iron1 found in red meat is the main factor enhancing colon cancer risk. Furthermore, they found that heme’s carcinogenetic effects originate in its interactions with dietary lipids, which lead to the formation of highly toxic compounds that kill off the colon’s epithelial cells. These findings will make it possible to fine-tune nutritional recommendations and establish effective dietary prevention strategies.

Infography: blood © Fotolia
By INRA News Office, translated by Jessica Pearce
Updated on 08/10/2015
Published on 08/10/2015

Colon cancer is the third most common type of cancer in the world. Colon cancer risk is estimated to climb by 18 to 20% when a person consumes an excessive amount of red or processed meat (i.e., more than 500 grams per week). There are several suspected carcinogens, namely heme iron1, heterocyclic amines produced by certain cooking methods, and endogenous N-nitroso compounds. However, until now, their relative contributions were unknown.

INRA researchers formed a collaboration with scientists at the National Veterinary School of Toulouse and the University of Reading in England to tackle this issue. First, they sought to identify the main carcinogen responsible for the development of colon cancer and to describe its functional mechanism. Their research has made a novel contribution to the field because, for the first time, researchers used nutritional doses of three different potential carcinogenic compounds. Using two different animal models and two different cell lines, the researchers were able to parse out the relative importance of heme iron (in the form of hemoglobin), heterocyclic amines, and endogenous N-nitroso compounds.

Using their specific experimental approach and animal models, the scientists were able to show that, by itself, the consumption of nutritional doses of heme iron in the form of hemoglobin can lead to an increased risk of colon cancer; no interactions were present with the other dietary factors tested.  Indeed, heme iron alone can increase the number of precancerous lesions that develop in rats. There were no additive or synergistic effects involving the other two classes of compounds. Furthermore, using an in vitro approach, the researchers discovered that the fecal water2 of rats that had received a heme-iron-enriched diet contained high levels of aldehydes (compounds produced from the iron-mediated oxidative degradation of dietary lipids). This fecal water had a toxic effect on normal colon cells but not on precancerous colon cells. Therefore, the consumption of heme iron may enhance colon cancer risk because it results in the production of aldehyde-enriched fecal water and thus selection for precancerous cells. More specifically, because these aldehydes have a genotoxic effect on normal cells, it is hypothesized that they may act as carcinogens, spurring the development of cancerous cells. Genotoxicity has also been observed in the intestinal mucus membrane of mice fed a heme-iron-rich diet.

This research, which was carried out using both animal models and cell lines (in vitro), highlights the central role played by heme iron (present in red and processed meats) in augmenting colon cancer risk. Furthermore, the results suggest that heme iron may function as a carcinogen because it mediates lipid peroxidation. These findings will make it possible to develop more detailed nutritional recommendations and establish effective, diet-based cancer-prevention strategies. For example, aldehyde formation could be limited through the consumption of processed meats enriched in antioxidants.

1 Heme iron is present in hemoglobin and myoglobin, which are found in the blood and muscles that make up meat. Indeed, 40% of meat is hemoglobin and myoglobin. Non-heme iron is found in other foods, namely plants, eggs, and dairy products.
2 the liquid, bioavailable component of feces

Contact(s)
Scientific contact(s):

Associated Division(s):
Nutrition, Chemical Food Safety and Consumer Behaviour
Associated Centre(s):
Occitanie-Toulouse

Reference

Nadia M. Bastide, Fatima Chenni, Marc Audebert, Raphaelle L. Santarelli, SylvianeTaché, Nathalie Naud, Maryse Baradat, Isabelle Jouanin, Reggie Surya, Ditte A. Hobbs, Gunter G. Kuhnle, Isabelle Raymond-Letron, Françoise Gueraud, Denis E. Corpet et Fabrice H.F. Pierre A Central Role for Heme Iron in Colon Carcinogenesis Associated with Red Meat Intake, Cancer research, January 2015 (DOI: 10.1158/0008- 5472.CAN-14-2554)

Taking calcium to prevent colon cancer

In 2013, this same team of INRA researchers studied the effects of calcium and α-tocopherol (a form of vitamin E) consumption in animals and healthy human volunteers. They found that adding calcium to a diet rich in processed meats or adding α-tocopherol directly to processed meats helped reduce colon cancer risk.

Reference: Fabrice HF Pierre, Océane CB Martin, Raphaelle L Santarelli, SylvianeTaché, Nathalie Naud, Françoise Guéraud, Marc Audebert, Jacques Dupuy, Nathalie Meunier, Didier Attaix, Jean-Luc Vendeuvre, Sidney S Mirvish, Gunter CG Kuhnle, Noel Cano, and Denis E Corpet Calcium and a-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers American Journal of Clinical Nutrition 2013; 98:1255–62.