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New Marker of Colon Cancer Risk Associated with Heme Intake: 1,4-Dihydroxynonane Mercapturic Acid

Pierre, Fabrice and Peiro, Géraldine and Taché, Sylviane and Cross, Amanda J. and Bingham, Sheila A. and Gasc, Nicole and Gottardi, Gaëlle and Corpet, Denis E. and Guéraud, Françoise New Marker of Colon Cancer Risk Associated with Heme Intake: 1,4-Dihydroxynonane Mercapturic Acid. (2006) Cancer Epidemiology Biomarkers and Prevention, 15. 2274-2279. ISSN 1055-9965

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Official URL: http://cebp.aacrjournals.org/cgi/reprint/15/11/2274


Background: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F2 (8-iso-PGF2), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. Methods: We measured urinary excretion of 8-iso-PGF2 and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron). Results: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF2 increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans. Conclusion: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2274–9)

Item Type:Article
Additional Information:Author can archive post-print after 12 months embargo (nov 2006 - nov 2007) Thanks to American Association for Cancer Research. The original PDF can be found at : http://cebp.aacrjournals.org/cgi/reprint/15/11/2274
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Institut National de la Recherche Agronomique - INRA (FRANCE)
Other partners > National Cancer Institute (USA)
Other partners > Medical Research Council (UNITED KINGDOM)
Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE)
Laboratory name:
Deposited On:18 Apr 2008 09:46

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