This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pierre, F. Articles by Guéraud, F. Search for Related Content PubMed PubMed Citation Articles by Pierre, F. Articles by Guéraud, F. Related Collections Risk Assessment Risk Assessment: Biomarkers

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

¹ Ecole Nationale Vétérinaire Toulouse and ² Institut National de la Recherche Agronomique, UMR INRA-ENVT 1089 Xénobiotiques, Toulouse, France; ³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; and ⁴ Medical Research Council, Dunn Human Nutrition Unit, Wellcome Trust/Medical Research Council Building, Cambridge, United Kingdom

Requests for reprints: Françoise Guéraud, Institut National de la Recherche Agronomique, UMR INRA-ENVT1089 Xénobiotiques, 180 chemin de Tournefeuille, 31931 Toulouse, France. Phone: 33-561-285-383; Fax: 33-561-285-244. E-mail: fgueraud{at}toulouse.inra.fr

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)

This article has been cited by other articles:

				F. Biasi, C. Mascia, and G. Poli The contribution of animal fat oxidation products to colon carcinogenesis, through modulation of TGF-{beta}1 signaling Carcinogenesis, May 1, 2008; 29(5): 890 - 894. [Abstract] [Full Text] [PDF]